1  4751 120 NOVEL RISK MARKERS FOR GASTRIC CANCER SCREENING: PRESENT STATUS AND FUTURE PROSPECTS. INITIAL IDENTIFICATION OF POPULATIONS AT HIGH RISK OF GASTRIC CANCER (GC) IS IMPORTANT FOR ENDOSCOPIC SCREENING OF GC. AS SERUM PEPSINOGEN (PG) TEST-POSITIVE SUBJECTS WITH PROGRESSION OF CHRONIC ATROPHIC GASTRITIS (CAG) SHOW A HIGH LIKELIHOOD OF FUTURE CANCER DEVELOPMENT, THIS POPULATION WARRANTS CAREFUL FOLLOW-UP OBSERVATION AS A HIGH-RISK GC GROUP. BY COMBINING THE PG TEST WITH HELICOBACTER PYLORI (HP) ANTIBODY TITERS, THE HP-RELATED CHRONIC GASTRITIS STAGE CAN BE CLASSIFIED, THUS IDENTIFYING NOT ONLY A GC HIGH-RISK GROUP BUT ALSO A LOW-RISK GROUP. AMONG PG TEST-NEGATIVE PATIENTS WITHOUT CAG, THOSE WITH HIGH SERUM PG II LEVELS AND HP ANTIBODY TITERS ARE THOUGHT TO HAVE SEVERE GASTRIC MUCOSAL INFLAMMATION AND THE RISK OF DIFFUSE-TYPE GC IS ALSO HIGH. MEANWHILE, IN GASTRIC MUCOSAE OBTAINED BY ENDOSCOPIC BIOPSY, HP INFECTION INDUCES ABERRANT DNA METHYLATION IN CPG ISLANDS IN MULTIPLE GENE REGIONS AND THE EXTENT OF METHYLATION CLEARLY CORRELATES WITH GC RISK. BY QUANTIFYING ABERRANT DNA METHYLATION IN SUITABLE GENE MARKERS, WE CAN DETERMINE THE EXTENT OF THE EPIGENETIC FIELD FOR CANCERIZATION. THESE NOVEL CONCEPTS AND RISK MARKERS WILL HAVE MANY CLINICAL APPLICATIONS IN GASTROINTESTINAL ENDOSCOPY, INCLUDING MORE EFFICIENT ENDOSCOPIC GC SCREENING AND A STRATEGIC APPROACH TO METACHRONOUS MULTIPLE GCS AFTER ENDOSCOPIC TREATMENT.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
2   672  34 BRAF, KRAS AND HELICOBACTER PYLORI EPIGENETIC CHANGES-ASSOCIATED CHRONIC GASTRITIS IN EGYPTIAN PATIENTS WITH AND WITHOUT GASTRIC CANCER. WE AIMED TO STUDY MLH1 AND MGMT METHYLATION STATUS IN HELICOBACTER PYLORI-ASSOCIATED CHRONIC GASTRITIS IN EGYPTIAN PATIENTS WITH AND WITHOUT GASTRIC CANCER. 39 PATIENTS WERE INCLUDED IN OUR STUDY. THEY WERE DIVIDED INTO 2 GROUPS; PATIENTS WITHOUT (GROUP I) AND WITH GASTRIC ADENOCARCINOMA (GROUP II). PATIENTS WERE SUBJECTED TO CLINICAL EXAMINATION, ABDOMINAL ULTRASOUND AND UPPER ENDOSCOPY FOR GASTRIC BIOPSY. BIOPSIES WERE SUBJECTED TO UREASE TEST, HISTOLOGICAL EXAMINATION, AND DNA PURIFICATION. H. PYLORI, BRAF, KRAS, MLH1 AND MGMT METHYLATION WERE ASSESSED BY QUANTITATIVE PCR. DNA SEQUENCING WAS PERFORMED TO ASSESS BRAF AND KRAS GENES MUTATION. QPCR OF H. PYLORI WAS SIGNIFICANTLY HIGHER IN PATIENTS WITH ADENOCARCINOMA (GROUP II) THAN THOSE WITHOUT ADENOCARCINOMA (GROUP I); WITH A P < 0.001 AS WELL AS IN PATIENTS WITH AGE ABOVE 50 YEARS WITH A P VALUE = 0.008. BY APPLYING LOGISTIC REGRESSION ANALYSIS IT WAS REPORTED THAT THE H. PYLORI QPCR IS A SIGNIFICANT PREDICTOR TO THE ADENOCARCINOMA WITH OR = 1.025 (95 % CI: 1. 002-1.048), WITH SENSITIVITY OF 90 % AND SPECIFICITY OF 100 %. ADENOCARCINOMA PATIENTS HAD A SIGNIFICANTLY HIGHER MEAN AGE AND LEVELS OF H. PYLORI, BRAF, K-RAS, METHYLATED MGMT AND METHYLATED MLH1 THAN THOSE OF GASTRITIS PATIENTS. DNA SEQUENCE ANALYSIS OF BRAF (CODON 12) AND KRAS (CODON 600) HAD GENES MUTATION IN GASTRIC ADENOCARCINOMA VERSUS CHRONIC GASTRITIS. CONCLUSION: H. PYLORI MAY CAUSE EPIGENETIC CHANGES PREDISPOSING THE PATIENTS TO CANCER STOMACH. ESTIMATION OF H. PYLORI BY QPCR CAN BE A GOOD PREDICTOR TO ADENOCARCINOMA. BRAF AND KRAS GENES MUTATION WERE REVELED IN GASTRITIS AND ADENOCARCINOMA PATIENTS.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
3  3222  45 HELICOBACTER PYLORI ASSOCIATED CHRONIC GASTRITIS, CLINICAL SYNDROMES, PRECANCEROUS LESIONS, AND PATHOGENESIS OF GASTRIC CANCER DEVELOPMENT. HELICOBACTER PYLORI (H. PYLORI) INFECTION IS WELL KNOWN TO BE ASSOCIATED WITH THE DEVELOPMENT OF PRECANCEROUS LESIONS SUCH AS CHRONIC ATROPHIC GASTRITIS (AG), OR GASTRIC INTESTINAL METAPLASIA (GIM), AND CANCER. VARIOUS MOLECULAR ALTERATIONS ARE IDENTIFIED NOT ONLY IN GASTRIC CANCER (GC) BUT ALSO IN PRECANCEROUS LESIONS. H. PYLORI TREATMENT SEEMS TO IMPROVE AG AND GIM, BUT STILL REMAINS CONTROVERSIAL. IN CONTRAST, MANY STUDIES, INCLUDING META-ANALYSIS, SHOW THAT H. PYLORI ERADICATION REDUCES GC. MOLECULAR MARKERS DETECTED BY GENETIC AND EPIGENETIC ALTERATIONS RELATED TO CARCINOGENESIS REVERSE FOLLOWING H. PYLORI ERADICATION. THIS INDICATES THAT THESE CHANGES MAY BE AN IMPORTANT FACTOR IN THE IDENTIFICATION OF HIGH RISK PATIENTS FOR CANCER DEVELOPMENT. PATIENTS WHO UNDERWENT ENDOSCOPIC TREATMENT OF GC ARE AT HIGH RISK FOR DEVELOPMENT OF METACHRONOUS GC. A RANDOMIZED CONTROLLED TRIAL FROM JAPAN CONCLUDED THAT PROPHYLACTIC ERADICATION OF H. PYLORI AFTER ENDOSCOPIC RESECTION SHOULD BE USED TO PREVENT THE DEVELOPMENT OF METACHRONOUS GC, BUT RECENT RETROSPECTIVE STUDIES DID NOT SHOW THE TENDENCY. PATIENTS WITH PRECANCEROUS LESIONS (MOLECULAR ALTERATIONS) THAT DO NOT REVERSE AFTER H. PYLORI TREATMENT, REPRESENT THE "POINT OF NO RETURN" AND MAY BE AT HIGH RISK FOR THE DEVELOPMENT OF GC. THEREFORE, EARLIER H. PYLORI ERADICATION SHOULD BE CONSIDERED FOR PREVENTING GC DEVELOPMENT PRIOR TO THE APPEARANCE OF PRECANCEROUS LESIONS.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
4  1797  31 EFFECT OF HELICOBACTER PYLORI ERADICATION ON GASTRIC PRECANCEROUS LESIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS. BACKGROUND: THE QUESTION OF WHETHER ERADICATION OF HELICOBACTER PYLORI (HP) CAN REVERSE GASTRIC PRECANCEROUS LESIONS, INCLUDING INTESTINAL METAPLASIA, REMAINS UNCERTAIN, LEADING TO ONGOING DEBATE. THEREFORE, A META-ANALYSIS WAS PERFORMED TO EVALUATE THE EFFECT OF HP ERADICATION ON GASTRIC PRECANCEROUS LESIONS. MATERIALS AND METHODS: PUBMED, EMBASE, COCHRANE LIBRARY, WEB OF SCIENCE, SCOPUS DATABASE, AND CLINICALTRIALS.GOV WERE SYSTEMATICALLY SEARCHED FROM INCEPTION TO APRIL 2023 FOR STUDIES THAT EXPLORED THE IMPACT OF HP ERADICATION ON GASTRIC PRECANCEROUS LESIONS. RISK RATIOS (RRS) AND THEIR 95% CONFIDENCE INTERVALS (95% CIS) WERE SELECTED AS THE EFFECT SIZE. WE USED THE RANDOM-EFFECTS MODEL TO ASSESS POOLED DATA. WE ALSO PERFORMED QUALITY ASSESSMENTS, SUBGROUP ANALYSES, AND SENSITIVITY ANALYSES. RESULTS: FIFTEEN STUDIES WERE INCLUDED. COMPARED WITH PLACEBO, HP ERADICATION COULD SIGNIFICANTLY PREVENT THE PROGRESSION OF GASTRIC PRECANCEROUS LESIONS (RR = 0.87, 95% CI: 0.81-0.94, P < 0.01) AND REVERSE THEM (RR = 1.32, 95% CI: 1.17-1.50, P < 0.01). THEN, SPECIFIC PRECANCEROUS LESIONS WERE FURTHER EXPLORED. THE PROGRESSION OF INTESTINAL METAPLASIA WAS SIGNIFICANTLY PREVENTED BY HP ERADICATION COMPARED TO PLACEBO OR NO TREATMENT (RR = 0.80, 95% CI: 0.69-0.94, P < 0.01). MOREOVER, COMPARED WITH PLACEBO OR NO TREATMENT, HP ERADICATION ALSO IMPROVED CHRONIC ATROPHIC GASTRITIS (RR = 1.84, 95% CI: 1.30-2.61, P < 0.01) AND INTESTINAL METAPLASIA (RR = 1.41, 95% CI: 1.15-1.73, P < 0.01). HOWEVER, IN TERMS OF PREVENTING DYSPLASIA PROGRESSION (RR = 0.86, 95% CI: 0.37-2.00) AND IMPROVING DYSPLASIA (RR = 0.89, 95% CI: 0.47-1.70), HP ERADICATION HAD NO ADVANTAGE COMPARED TO PLACEBO OR NO TREATMENT. CONCLUSIONS: HP ERADICATION THERAPY COULD PREVENT THE PROGRESSION OF GASTRIC PRECANCEROUS LESIONS AND REVERSE THEM. NOTABLY, INTESTINAL METAPLASIA CAN BE REVERSED, BUT THIS MAY ONLY BE APPROPRIATE FOR PATIENTS WITH EPIGENETIC ALTERATIONS AND MILDER LESIONS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
5  1322  37 DEMONSTRATION OF THE USEFULNESS OF EPIGENETIC CANCER RISK PREDICTION BY A MULTICENTRE PROSPECTIVE COHORT STUDY. BACKGROUND: EPIGENETIC ALTERATIONS ACCUMULATE IN NORMAL-APPEARING TISSUES OF PATIENTS WITH CANCER, PRODUCING AN EPIGENETIC FIELD DEFECT. CROSS-SECTIONAL STUDIES SHOW THAT THE DEGREE OF THE DEFECT MAY BE ASSOCIATED WITH RISK IN SOME TYPES OF CANCER, ESPECIALLY CANCERS ASSOCIATED WITH CHRONIC INFLAMMATION. OBJECTIVE: TO DEMONSTRATE, BY A MULTICENTRE PROSPECTIVE COHORT STUDY, THAT THE RISK OF METACHRONOUS GASTRIC CANCER AFTER ENDOSCOPIC RESECTION (ER) CAN BE PREDICTED BY ASSESSMENT OF THE EPIGENETIC FIELD DEFECT USING METHYLATION LEVELS. DESIGN: PATIENTS WITH EARLY GASTRIC CANCER, AGED 40-80 YEARS, WHO PLANNED TO HAVE, OR HAD UNDERGONE, ER, WERE ENROLLED AT LEAST 6 MONTHS AFTER HELICOBACTER PYLORI INFECTION DISCONTINUED. METHYLATION LEVELS OF THREE PRESELECTED GENES (MIR-124A-3, EMX1 AND NKX6-1) WERE MEASURED BY QUANTITATIVE METHYLATION-SPECIFIC PCR. PATIENTS WERE FOLLOWED UP ANNUALLY BY ENDOSCOPY, AND THE PRIMARY ENDPOINT WAS DEFINED AS DETECTION OF A METACHRONOUS GASTRIC CANCER. AUTHENTIC METACHRONOUS GASTRIC CANCERS WERE DEFINED AS CANCERS EXCLUDING THOSE DETECTED WITHIN 1 YEAR AFTER THE ENROLMENT. RESULTS: AMONG 826 PATIENTS ENROLLED, 782 PATIENTS HAD AT LEAST ONE FOLLOW-UP, WITH A MEDIAN FOLLOW-UP OF 2.97 YEARS. AUTHENTIC METACHRONOUS GASTRIC CANCERS DEVELOPED IN 66 PATIENTS: 29, 16 AND 21 PATIENTS AT 1-2, 2-3 AND >/=3 YEARS AFTER THE ENROLMENT, RESPECTIVELY. THE HIGHEST QUARTILE OF THE MIR-124A-3 METHYLATION LEVEL HAD A SIGNIFICANT UNIVARIATE HR (95% CI) (2.17 (1.07 TO 4.41); P=0.032) AND A MULTIVARIATE-ADJUSTED HR (2.30 (1.03 TO 5.10); P=0.042) OF DEVELOPING AUTHENTIC METACHRONOUS GASTRIC CANCERS. SIMILAR TRENDS WERE SEEN FOR EMX1 AND NKX6-1. CONCLUSIONS: ASSESSMENT OF THE DEGREE OF AN EPIGENETIC FIELD DEFECT IS A PROMISING CANCER RISK MARKER THAT TAKES ACCOUNT OF LIFE HISTORY.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
6  3134  45 GLOBAL DNA HYPOMETHYLATION IS AN EARLY EVENT IN HELICOBACTER PYLORI-RELATED GASTRIC CARCINOGENESIS. AIM: CANCER, PARTICULARLY GASTRIC CANCER (GC), IS PREVALENTLY AN EPIGENETIC PHENOMENON THAT IS DEPENDENT ON AN ALTERED DNA METHYLATION PATTERN. IN GASTRIC CARCINOGENESIS, MANY GENES SHOW ABERRANT METHYLATION; HOWEVER, NONE OF THEM MAY BE USED AS A BIOMARKER OF CANCER RISK AND PROGRESSION. THE AUTHORS AIMED TO EVALUATE THE GLOBAL DNA METHYLATION OF GASTRIC MUCOSA IN HELICOBACTER PYLORI (HP)-RELATED CHRONIC GASTRITIS, IN GC AND IN 10 PATIENTS WITH PRENEOPLASTIC LESIONS (IE, ATROPHY AND INTESTINAL METAPLASIA) FOLLOWED UP FOR 10 YEARS. METHODS: THE AUTHORS ANALYSED 93 DYSPEPTIC PATIENTS WHO UNDERWENT UPPER ENDOSCOPY, 41 SURGICAL GC SAMPLES AND 10 PATIENTS WITH PRENEOPLASTIC GASTRIC LESIONS FOLLOWED UP FOR 10 YEARS AFTER SUCCESSFUL HP ERADICATION THERAPY. GLOBAL DNA METHYLATION STATUS AND SURROGATE MARKERS OF CELL PROLIFERATION AND APOPTOSIS WERE EVALUATED BY IMMUNOHISTOCHEMISTRY USING THE ANTI-5-METHYLCYTOSINE (5-MC), ANTI-KI-67 AND ANTI-P53 (ANTI-APOPTOTIC MARKER)-SPECIFIC ANTIBODIES, RESPECTIVELY. RESULTS: GLOBAL DNA METHYLATION OF GASTRIC MUCOSA GRADUALLY DECREASED FROM NORMAL MUCOSA TO HP-POSITIVE GASTRITIS, HP-POSITIVE CHRONIC ATROPHIC GASTRITIS, INDEPENDENT OF CAG-A STATUS AND GC; HOWEVER, THE VARIATION WAS SIGNIFICANT (P<0.05) ONLY BETWEEN HP-NEGATIVE SUBJECTS AND HP-POSITIVE CHRONIC GASTRITIS. INTERESTINGLY, THE 5-MC IMMUNOSTAINING WAS ABSENT IN AREAS OF INTESTINAL METAPLASIA. IN THE 10 PATIENTS WITH PRENEOPLASTIC LESIONS, GLOBAL DNA METHYLATION DECREASED OVER TIME DESPITE THE ERADICATION OF HP INFECTION, BUT REACHED SIGNIFICANCE ONLY AT 10 YEARS VERSUS BASELINE. THE 5-MC IMMUNOSTAINING NEGATIVELY CORRELATED WITH KI-67 AND P53 EXPRESSION IN ALL GROUPS. CONCLUSION: GLOBAL DNA HYPOMETHYLATION IS AN EARLY MOLECULAR EVENT IN HP-RELATED GASTRIC CARCINOGENESIS. FURTHER STUDIES WITH MORE CASES AND A LONGER FOLLOW-UP ARE NEEDED TO ESTABLISH THE POTENTIAL GC PREDICTIVE ROLE OF DNA HYPOMETHYLATION.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
7  3413  26 HSA-MIR-29C AND HSA-MIR-135B DIFFERENTIAL EXPRESSION AS POTENTIAL BIOMARKER OF GASTRIC CARCINOGENESIS. AIM: TO INVESTIGATE THE EXPRESSION PROFILES OF HSA-MIR-29C AND HSA-MIR-135B IN GASTRIC MUCOSAL SAMPLES AND THEIR VALUES AS GASTRIC CARCINOGENESIS BIOMARKERS. METHODS: THE EXPRESSION LEVELS OF HSA-MIR-29C AND HSA-MIR-135B IN NORMAL GASTRIC MUCOSA, NON-ATROPHIC CHRONIC GASTRITIS, INTESTINAL METAPLASIA AND INTESTINAL-TYPE GASTRIC ADENOCARCINOMA WERE ANALYSED USING QUANTITATIVE REAL-TIME PCR. THE DIFFERENCE BETWEEN HSA-MIR-29C AND HSA-MIR-135B EXPRESSION PROFILES IN THE GROUPED SAMPLES WAS EVALUATED BY ANOVA AND STUDENT'S T-TEST TESTS. THE RESULTS WERE ADJUSTED FOR MULTIPLE TESTING BY USING BONFERRONI'S CORRECTION. P VALUES </= 0.05 WERE CONSIDERED STATISTICALLY SIGNIFICANT. TO EVALUATE HSA-MIR-29C AND HSA-MIR-135B EXPRESSIONS AS POTENTIAL BIOMARKERS OF GASTRIC CARCINOGENESIS, WE PERFORMED A RECEIVER OPERATING CHARACTERISTIC CURVE ANALYSIS AND THE DERIVED AREA UNDER THE CURVE, AND A CATEGORICAL PRINCIPAL COMPONENTS ANALYSIS. IN SILICO IDENTIFICATION OF THE GENETIC TARGETS OF HSA-MIR-29C AND HSA-MIR-135B WAS PERFORMED USING DIFFERENT PREDICTION TOOLS, IN ORDER TO IDENTIFY POSSIBLE GENES INVOLVED IN GASTRIC CARCINOGENESIS. RESULTS: THE EXPRESSION LEVELS OF HSA-MIR-29C WERE HIGHER IN NORMAL GASTRIC MUCOSAL SAMPLES, AND DECREASED PROGRESSIVELY IN NON-ATROPHIC CHRONIC GASTRITIS SAMPLES, INTESTINAL METAPLASIA SAMPLES AND INTESTINAL-TYPE GASTRIC ADENOCARCINOMA SAMPLES. THE EXPRESSION OF HSA-MIR-29C IN THE GASTRIC LESIONS SHOWED THAT NON-ATROPHIC GASTRITIS HAVE AN INTERMEDIATE PROFILE TO GASTRIC NORMAL MUCOSA AND INTESTINAL-TYPE GASTRIC ADENOCARCINOMA, AND THAT INTESTINAL METAPLASIA SAMPLES PRESENTED AN EXPRESSION PATTERN SIMILAR TO THAT IN INTESTINAL-TYPE GASTRIC ADENOCARCINOMA. THIS MICRORNA (MIRNA) HAS A GOOD DISCRIMINATORY ACCURACY BETWEEN NORMAL GASTRIC SAMPLES AND (1) INTESTINAL-TYPE GASTRIC ADENOCARCINOMA; AND (2) INTESTINAL METAPLASIA, AND REGULATES THE DMNT3A ONCOGENE. HSA-MIR-135B IS UP-REGULATED IN NON-ATROPHIC CHRONIC GASTRITIS AND INTESTINAL METAPLASIA SAMPLES AND DOWN-REGULATED IN NORMAL GASTRIC MUCOSA AND INTESTINAL-TYPE GASTRIC ADENOCARCINOMA SAMPLES. NON-ATROPHIC CHRONIC GASTRITIS AND INTESTINAL METAPLASIA ARE SIGNIFICANTLY DIFFERENT FROM NORMAL GASTRIC MUCOSA SAMPLES. HSA-MIR-135B EXPRESSION PRESENTED A GREATER DISCRIMINATORY ACCURACY BETWEEN NORMAL SAMPLES AND GASTRIC LESIONS. THIS MIRNA WAS ASSOCIATED WITH HELICOBACTER PYLORI PRESENCE IN NON-ATROPHIC CHRONIC GASTRITIS SAMPLES AND REGULATES THE APC AND KLF4 TUMOUR SUPPRESSOR GENES. CONCLUSION: OUR RESULTS PROVIDE EVIDENCE OF EPIGENETIC ALTERATIONS IN NON-ATROPHIC CHRONIC GASTRITIS AND INTESTINAL METAPLASIA AND SUGGEST THAT HSA-MIR-29C AND HSA-MIR-135B ARE PROMISING BIOMARKERS OF GASTRIC CARCINOGENESIS.	2016	
                                                                                                                                                                             
8  2439  31 EPIGENETIC SILENCING OF THE MLH1 PROMOTER IN RELATION TO THE DEVELOPMENT OF GASTRIC CANCER AND ITS USE AS A BIOMARKER FOR PATIENTS WITH MICROSATELLITE INSTABILITY: A SYSTEMATIC ANALYSIS. BACKGROUND/AIMS: HUMAN MUTL HOMOLOG 1 (MLH1) PROMOTER METHYLATION WAS REPORTED IN GASTRIC CANCER (GC). THIS STUDY DETERMINED THE CLINICOPATHOLOGICAL, PROGNOSTIC, AND DIAGNOSTIC EFFECTS OF MLH1 PROMOTER METHYLATION IN GC. METHODS: THE COMBINED ODDS RATIO (OR) OR HAZARD RATIO (HR) AND THEIR CORRESPONDING 95% CONFIDENCE INTERVALS (95% CI) WERE CALCULATED. THE POOLED SENSITIVITY, SPECIFICITY, AND AREA UNDER THE CURVE (AUC) WERE ANALYZED. RESULTS: A TOTAL OF 4654 GC PATIENTS AND 3669 NON-MALIGNANT CONTROLS WERE IDENTIFIED IN THIS SYSTEMATIC ANALYSIS. MLH1 PROMOTER METHYLATION WAS SIGNIFICANTLY HIGHER IN GC SAMPLES THAN IN GASTRIC ADENOMAS, CHRONIC GASTRITIS, ADJACENT TISSUES, NORMAL GASTRIC MUCOSA, AND NORMAL HEALTHY BLOOD SAMPLES, BUT IT EXHIBITED A SIMILAR FREQUENCY IN GC VS. INTESTINAL METAPLASIA AND DYSPLASIA SAMPLES. MLH1 PROMOTER METHYLATION CORRELATED WITH AGE AND MICROSATELLITE INSTABILITY (MSI), BUT IT WAS NOT ASSOCIATED WITH GENDER, H. PYLORI INFECTION, SMOKING, DRINKING BEHAVIORS, PATHOLOGICAL HISTOLOGY, TUMOR DIFFERENTIATION, CLINICAL STAGE, LYMPH NODE STATUS, DISTANT METASTASIS, OR OVERALL SURVIVAL OF GC. MLH1 PROMOTER METHYLATION EXHIBITED A POOR SENSITIVITY VALUE (< 0.5) IN PATIENTS WITH GC COMPARED WITH ADJACENT TISSUES, GASTRIC ADENOMAS, CHRONIC GASTRITIS, NORMAL GASTRIC MUCOSA, AND NORMAL HEALTHY BLOOD SAMPLES. THE POOLED SENSITIVITY, SPECIFICITY, AND AUC OF MLH1 PROMOTER METHYLATION IN GC WITH MSI VS. GC WITH MICROSATELLITE STABILITY (MSS) SAMPLES WERE 0.64, 0.96, AND 0.90, RESPECTIVELY. CONCLUSIONS: OUR RESULTS SUGGEST THAT THE DETECTION OF MLH1 PROMOTER METHYLATION MAY BE A POTENTIAL PROGNOSTIC BIOMARKER FOR GC PATIENTS WITH MSI.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
9  3227  35 HELICOBACTER PYLORI INFECTION-INDUCED H3SER10 PHOSPHORYLATION IN STEPWISE GASTRIC CARCINOGENESIS AND ITS CLINICAL IMPLICATIONS. BACKGROUND: OUR PREVIOUS WORKS HAVE DEMONSTRATED THAT HELICOBACTER PYLORI (HP) INFECTION CAN ALTER HISTONE H3 SERINE 10 PHOSPHORYLATION STATUS IN GASTRIC EPITHELIAL CELLS. HOWEVER, WHETHER HELICOBACTER PYLORI-INDUCED HISTONE H3 SERINE 10 PHOSPHORYLATION PARTICIPATES IN GASTRIC CARCINOGENESIS IS UNKNOWN. WE INVESTIGATE THE EXPRESSION OF HISTONE H3 SERINE 10 PHOSPHORYLATION IN VARIOUS STAGES OF GASTRIC DISEASE AND EXPLORE ITS CLINICAL IMPLICATION. MATERIALS AND METHODS: STOMACH BIOPSY SAMPLES FROM 129 PATIENTS WERE COLLECTED AND STAINED WITH HISTONE H3 SERINE 10 PHOSPHORYLATION, KI67, AND HELICOBACTER PYLORI BY IMMUNOHISTOCHEMISTRY STAINING, EXPRESSED AS LABELING INDEX. THEY WERE CATEGORIZED INTO NONATROPHIC GASTRITIS, CHRONIC ATROPHIC GASTRITIS, INTESTINAL METAPLASIA, LOW-GRADE INTRAEPITHELIAL NEOPLASIA, HIGH-GRADE INTRAEPITHELIAL NEOPLASIA, AND INTESTINAL-TYPE GASTRIC CANCER GROUPS. HELICOBACTER PYLORI INFECTION WAS DETERMINED BY EITHER (13) C-UREA BREATH TEST OR IMMUNOHISTOCHEMISTRY STAINING. RESULTS: IN HELICOBACTER PYLORI-NEGATIVE PATIENTS, LABELING INDEX OF HISTONE H3 SERINE 10 PHOSPHORYLATION WAS GRADUALLY INCREASED IN NONATROPHIC GASTRITIS, CHRONIC ATROPHIC GASTRITIS, INTESTINAL METAPLASIA GROUPS, PEAKED AT LOW-GRADE INTRAEPITHELIAL NEOPLASIA, AND DECLINED IN HIGH-GRADE INTRAEPITHELIAL NEOPLASIA AND GASTRIC CANCER GROUPS. IN HELICOBACTER PYLORI-INFECTED PATIENTS, LABELING INDEX OF HISTONE H3 SERINE 10 PHOSPHORYLATION FOLLOWED THE SIMILAR PATTERN AS ABOVE, WITH INCREASED EXPRESSION OVER THE CORRESPONDING HELICOBACTER PYLORI-NEGATIVE CONTROLS EXCEPT IN NONATROPHIC GASTRITIS PATIENT WHOSE LABELING INDEX WAS DECREASED WHEN COMPARED WITH HELICOBACTER PYLORI-NEGATIVE CONTROL. LABELING INDEX OF KI67 IN HELICOBACTER PYLORI-NEGATIVE GROUPS WAS HIGHER IN GASTRIC CANCER THAN CHRONIC ATROPHIC GASTRITIS AND LOW-GRADE INTRAEPITHELIAL NEOPLASIA GROUPS, AND HIGHER IN INTESTINAL METAPLASIA GROUP COMPARED WITH CHRONIC ATROPHIC GASTRITIS GROUP. IN HELICOBACTER PYLORI-POSITIVE GROUPS, KI67 LABELING INDEX WAS INCREASED STEPWISE FROM NONATROPHIC GASTRITIS TO GASTRIC CANCER EXCEPT SLIGHTLY DECREASE IN CHRONIC ATROPHIC GASTRITIS GROUP. IN ADDITION, WE NOTED THAT HISTONE H3 SERINE 10 PHOSPHORYLATION STAINING IS ACCOMPANIED WITH ITS LOCATION CHANGES FROM GASTRIC GLAND BOTTOM EXPANDED TO WHOLE GLAND AS DISEASE STAGE PROGRESS. CONCLUSIONS: THESE RESULTS INDICATE THAT STEPWISE GASTRIC CARCINOGENESIS IS ASSOCIATED WITH ALTERED HISTONE H3 SERINE 10 PHOSPHORYLATION, HELICOBACTER PYLORI INFECTION ENHANCES HISTONE H3 SERINE 10 PHOSPHORYLATION EXPRESSION IN THESE PROCESSES; IT IS ALSO ACCOMPANIED WITH HISTONE H3 SERINE 10 PHOSPHORYLATION LOCATION CHANGE FROM GLAND BOTTOM STAINING EXPAND TO WHOLE GLAND EXPRESSION. THE RESULTS SUGGEST THAT EPIGENETIC DYSREGULATION MAY PLAY IMPORTANT ROLES IN HELICOBACTER PYLORI-INDUCED GASTRIC CANCER.	2018	

10  1830  34 EFFECTS OF LONG-TERM ASPIRIN USE ON MOLECULAR ALTERATIONS IN PRECANCEROUS GASTRIC MUCOSA IN PATIENTS WITH AND WITHOUT GASTRIC CANCER. THE RISK OF GASTRIC CANCER (GC) REMAINS EVEN AFTER H. PYLORI ERADICATION; THUS, OTHER COMBINATION TREATMENTS, SUCH AS CHEMOPREVENTIVE DRUGS, ARE NEEDED. WE EVALUATED THE EFFECTS OF ASPIRIN ON GENETIC/EPIGENETIC ALTERATIONS IN PRECANCEROUS CONDITIONS, I.E., ATROPHIC MUCOSA (AM) AND INTESTINAL METAPLASIA (IM), IN PATIENTS WITH CHRONIC GASTRITIS WHO HAD TAKEN ASPIRIN FOR MORE THAN 3 YEARS. A TOTAL OF 221 BIOPSY SPECIMENS FROM 74 PATIENTS, INCLUDING ATROPHIC GASTRITIS (AG) CASES WITHOUT ASPIRIN USE (CONTROL), AG CASES WITH ASPIRIN USE (AG GROUP), AND GC CASES WITH ASPIRIN USE (GC GROUP), WERE ANALYZED. ASPIRIN USE WAS ASSOCIATED WITH A SIGNIFICANT REDUCTION OF CDH1 METHYLATION IN AM (OR: 0.15, 95% CI: 0.06-0.41, P = 0.0002), BUT WAS LESS EFFECTIVE IN REVERSING THE METHYLATION THAT OCCURRED IN IM. FREQUENT HYPERMETHYLATION INCLUDING THAT OF CDH1 IN AM INCREASED IN THE GC GROUP COMPARED TO THE AG GROUP, AND CDH1 METHYLATION WAS AN INDEPENDENT PREDICTIVE MARKER OF GC (OR: 8.50, 95% CI: 2.64-25.33, P = 0.0003). IN PATIENTS WITH LONG-TERM ASPIRIN USE, THE CHANGES OF MOLECULAR EVENTS IN AM BUT NOT IM MAY BE AN IMPORTANT FACTOR IN THE REDUCTION OF CANCER INCIDENCE. IN ADDITION, METHYLATION OF THE CDH1 GENE IN AM MAY BE A SURROGATE OF GC.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
11  3232  29 HELICOBACTER PYLORI-INDUCED SIGNALING PATHWAYS CONTRIBUTE TO INTESTINAL METAPLASIA AND GASTRIC CARCINOGENESIS. HELICOBACTER PYLORI (H. PYLORI) INDUCES CHRONIC GASTRIC INFLAMMATION, ATROPHIC GASTRITIS, INTESTINAL METAPLASIA, AND CANCER. ALTHOUGH THE RISK OF GASTRIC CANCER INCREASES EXPONENTIALLY WITH THE EXTENT OF ATROPHIC GASTRITIS, THE PRECISE MECHANISMS OF GASTRIC CARCINOGENESIS HAVE NOT BEEN FULLY ELUCIDATED. H. PYLORI INDUCES GENETIC AND EPIGENETIC CHANGES IN GASTRIC EPITHELIAL CELLS THROUGH ACTIVATING INTRACELLULAR SIGNALING PATHWAYS IN A CAGPAI-DEPENDENT MANNER. H. PYLORI EVENTUALLY INDUCES GASTRIC CANCER WITH CHROMOSOMAL INSTABILITY (CIN) OR MICROSATELLITE INSTABILITY (MSI), WHICH ARE CLASSIFIED AS TWO MAJOR SUBTYPES OF GASTRIC CANCER. ELUCIDATION OF THE PRECISE MECHANISMS OF GASTRIC CARCINOGENESIS WILL ALSO BE IMPORTANT FOR CANCER THERAPY.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
12  3231  28 HELICOBACTER PYLORI-INDUCED MODULATION OF THE PROMOTER METHYLATION OF WNT ANTAGONIST GENES IN GASTRIC CARCINOGENESIS. BACKGROUND: THIS STUDY AIMED TO INVESTIGATE THE CHANGES IN THE PROMOTER METHYLATION AND GENE EXPRESSION OF MULTIPLE WNT ANTAGONISTS BETWEEN THE CHRONIC INFECTION AND ERADICATION OF HELICOBACTER PYLORI (H. PYLORI) IN GASTRIC CARCINOGENESIS. METHODS: THE LEVELS OF METHYLATION AND CORRESPONDING MRNA EXPRESSION OF SEVEN WNT ANTAGONIST GENES (SFRP1, -2, -5, DKK1, -2, -3, WIF1) WERE COMPARED AMONG THE PATIENTS WITH H. PYLORI-POSITIVE GASTRIC CANCERS (GCS), AND H. PYLORI-POSITIVE AND H. PYLORI-NEGATIVE CONTROLS, BY QUANTITATIVE METHYLIGHT ASSAY AND REAL-TIME REVERSE TRANSCRIPTION (RT)-POLYMERASE CHAIN REACTION (PCR), RESPECTIVELY. THE CHANGES OF THE METHYLATION AND EXPRESSION LEVELS OF THE GENES WERE ALSO COMPARED BETWEEN THE H. PYLORI ERADICATION AND H. PYLORI-PERSISTENT GROUPS 1 YEAR AFTER ENDOSCOPIC RESECTION OF GCS. RESULTS: THE METHYLATION LEVELS OF SFRP AND DKK FAMILY GENES WERE SIGNIFICANTLY INCREASED IN THE PATIENTS WITH H. PYLORI-POSITIVE GCS AND FOLLOWED BY H. PYLORI-POSITIVE CONTROLS COMPARED WITH H. PYLORI-NEGATIVE CONTROLS (P < 0.001). SFRP1, -2, AND DKK3 GENE EXPRESSION WAS STEPWISE DOWNREGULATED FROM H. PYLORI-NEGATIVE CONTROLS, H. PYLORI-POSITIVE CONTROLS, AND TO H. PYLORI-POSITIVE GCS (P < 0.05). AMONG THE WNT ANTAGONISTS, ONLY THE DEGREES OF METHYLATION AND DOWNREGULATION OF DKK3 WERE SIGNIFICANTLY REDUCED AFTER H. PYLORI ERADICATION (P < 0.05). CONCLUSION: EPIGENETIC SILENCING OF SFRP AND DKK FAMILY GENES MAY FACILITATE THE FORMATION OF AN EPIGENETIC FIELD DURING H. PYLORI-ASSOCIATED GASTRIC CARCINOGENESIS. THE EPIGENETIC FIELD MAY NOT BE REVERSED EVEN AFTER H. PYLORI ERADICATION EXCEPT BY DKK3 METHYLATION.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
13   526  36 ASSOCIATIONS OF HELICOBACTER PYLORI INFECTION AND CHRONIC ATROPHIC GASTRITIS WITH ACCELERATED EPIGENETIC AGEING IN OLDER ADULTS. BACKGROUND: HELICOBACTER PYLORI (HP) INFECTION AND CHRONIC ATROPHIC GASTRITIS (CAG) HAVE SHOWN STRONG ASSOCIATIONS WITH THE DEVELOPMENT OF GASTRIC CANCER. THIS STUDY AIMED TO EXAMINE WHETHER BOTH RISK FACTORS ARE ASSOCIATED WITH ACCELERATED EPIGENETIC AGEING, AS DETERMINED BY THE 'DNA METHYLATION AGE', IN A POPULATION-BASED STUDY OF OLDER ADULTS (N=1477). METHODS: SEROLOGICAL MEASUREMENTS OF HP ANTIBODIES AND PEPSINOGEN I AND II FOR CAG DEFINITION WERE OBTAINED BY ELISA KITS. WHOLE BLOOD DNA METHYLATION PROFILES WERE MEASURED BY ILLUMINA HUMAN METHYLATION450K BEADCHIP. DNA METHYLATION AGES WERE CALCULATED BY TWO ALGORITHMS PROPOSED BY HORVATH AND HANNUM ET AL. RESULTS: AFTER ADJUSTING FOR POTENTIAL COVARIATES IN LINEAR REGRESSION MODELS, WE FOUND THAT HP INFECTION, INFECTION WITH VIRULENT HP STRAINS (CAGA+) AND SEVERE CAG WERE SIGNIFICANTLY ASSOCIATED WITH AN INCREASE IN DNA METHYLATION AGE BY APPROXIMATELY 0.4, 0.6 AND 1 YEAR (ALL P-VALUES <0.05), RESPECTIVELY. CONCLUSIONS: OUR STUDY INDICATES THAT BOTH CAGA+ HP INFECTION AND CAG GO ALONG WITH ACCELERATED EPIGENETIC AGEING.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
14  1056  32 CLINICAL MANIFESTATIONS AND EPIGENETIC MECHANISMS OF GASTRIC MUCOSA ASSOCIATED LYMPHOID TISSUE LYMPHOMA AND LONG-TERM FOLLOW-UP FOLLOWING HELICOBACTER PYLORI ERADICATION. THE CURRENT STUDY AIMED TO SUMMARIZE THE CLINICAL MANIFESTATIONS AND IDENTIFY THE EPIGENETIC MECHANISMS OF GASTRIC MUCOSA ASSOCIATED LYMPHOID TISSUE (MALT) LYMPHOMA, AS WELL AS EVALUATE THE LONG-TERM EFFECTS OF HELICOBACTER PYLORI (H. PYLORI) ERADICATION. A TOTAL OF 122 PATIENTS WITH MARGINAL ZONE B-CELL LYMPHOMA OF PRIMARY GASTRIC MALT LYMPHOMA WERE ENROLLED IN THE PRESENT STUDY. THE CLINICAL MANIFESTATIONS OF GASTRIC MALT LYMPHOMA, INCLUDING SYMPTOMS, H. PYLORI STATE AND ENDOSCOPIC TYPE, WERE SUMMARIZED. THE RESPONSE TO THERAPY WAS EVALUATED IN PATIENTS THAT UNDERWENT H. PYLORI ERADICATION. SURVIVAL ANALYSIS WAS ESTIMATED USING THE KAPLAN-MEIER METHOD. THE EXPRESSION OF MICRORNA-383 (MIR-383) IN TUMOR TISSUES AND CELL LINES WAS DETERMINED USING REVERSE TRANSCRIPTION QUANTITATIVE POLYMERASE CHAIN REACTION. FURTHERMORE, BIOINFORMATIC ANALYSES, LUCIFERASE REPORTER ASSAYS. AND WESTERN BLOT ANALYSIS IDENTIFIED ZINC FINGER E-BOX BINDING HOMEOBOX 2 (ZEB2) AS A DIRECT TARGET GENE OF MIR-383. AN MTT ASSAY WAS USED TO EXAMINE THE FUNCTION OF MIR-383 AND ZEB2 IN MALT LYMPHOMA. THE CLINICAL SYMPTOMS OF PATIENTS WITH GASTRIC MALT LYMPHOMA WERE NON-SPECIFIC AND INCLUDED EPIGASTRIC PAIN, ABDOMINAL DISCOMFORT AND BLEEDING. THE MAJORITY OF ENDOSCOPIC TYPES WERE CLASSIFIED AS ULCER, EROSION AND MUCOSA EDEMA. THE H. PYLORI INFECTION RATE WAS 79.5% (97/122) AND A TOTAL OF 47 PATIENTS UNDERWENT ERADICATION THERAPY. LYMPHOMA REMISSION WAS ACHIEVED IN 93.6% (44/47) OF PATIENTS AND COMPLETE REMISSION (CR) WAS ACHIEVED IN 74.4% (35/47). THE MEDIAN FOLLOW-UP TIME WAS 38 MONTHS (RANGE, 10-132 MONTHS) AND THE MEDIAN TIME TAKEN TO ACHIEVE CR WAS 4 MONTHS (RANGE, 3-7 MONTHS). THE ESTIMATED 3-YEAR SURVIVAL RATE WAS 90.3% AND THE 5-YEAR SURVIVAL RATE WAS 76.2%. THEREFORE, IT WAS DETERMINED THAT PATIENTS WITH STAGE I OR II GASTRIC MALT LYMPHOMA ARE ABLE TO UNDERGO H. PYLORI ERADICATION AS A FIRST-LINE TREATMENT AND THAT THE SURVIVAL RATE OF PATIENTS UNDERGOING THIS TREATMENT IS HIGH. FURTHERMORE, IT WAS DETERMINED THAT THE MECHANISM BY WHICH MIR-383 AND ZEB2 CONTRIBUTE TO MALT LYMPHOMA PROGRESSION IS BY THE TARGETING OF ZEB2 BY MIR-383, WHICH INHIBITS THE PROLIFERATION OF CANCER CELLS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
15  2895  34 GASTRIC CANCER DEVELOPMENT AFTER THE SUCCESSFUL ERADICATION OF HELICOBACTER PYLORI. GASTRIC CANCER (GC) DEVELOPS AS A RESULT OF INFLAMMATION-ASSOCIATED CARCINOGENESIS DUE TO HELICOBACTER PYLORI (H. PYLORI) INFECTION AND SUBSEQUENT DEFECTS IN GENETIC/EPIGENETIC EVENTS. ALTHOUGH THE INDICATION FOR ERADICATION THERAPY HAS BECOME WIDESPREAD, CLINICAL STUDIES HAVE REVEALED ITS LIMITED EFFECTS IN DECREASING THE INCIDENCE OF GC. MOREOVER, RESEARCH ON BIOPSY SPECIMENS OBTAINED BY CONVENTIONAL ENDOSCOPY HAS DEMONSTRATED THE FEASIBILITY OF THE RESTORATION OF SOME GENETIC/EPIGENETIC ALTERATIONS IN THE GASTRIC MUCOSA. PRACTICALLY, THE NUMBER OF SPORADIC CASES OF PRIMARY/METACHRONOUS GC THAT EMERGE AFTER SUCCESSFUL ERADICATION HAS INCREASED, WHILE ON-GOING GUIDELINES RECOMMEND ERADICATION THERAPY FOR PATIENTS WITH CHRONIC GASTRITIS AND THOSE WITH BACKGROUND MUCOSA AFTER ENDOSCOPIC RESECTION FOR GC. ACCORDINGLY, REGULAR SURVEILLANCE OF NUMEROUS INDIVIDUALS WHO HAVE RECEIVED ERADICATION THERAPY IS RECOMMENDED DESPITE THE LACK OF BIOMARKERS. RECENTLY, THE FOCUS HAS BEEN ON FUNCTIONAL REVERSIBILITY AFTER SUCCESSFUL ERADICATION AS ANOTHER CUE TO ELUCIDATE THE MECHANISMS OF RESTORATION AS WELL AS THOSE OF CARCINOGENESIS IN THE GASTRIC MUCOSA AFTER H. PYLORI ERADICATION. WE DEMONSTRATED THAT CONGO-RED CHROMOENDOSCOPY ENABLED THE IDENTIFICATION OF THE MULTI-FOCAL DISTRIBUTION OF FUNCTIONALLY IRREVERSIBLE MUCOSA COMPARED WITH THAT OF RESTORED MUCOSA AFTER SUCCESSFUL ERADICATION IN INDIVIDUALS AT EXTREMELY HIGH RISK FOR GC. FURTHER RESEARCH THAT USES FUNCTIONAL IMAGING MAY PROVIDE NEW INSIGHTS INTO THE MECHANISMS OF REGENERATION AND CARCINOGENESIS IN THE GASTRIC MUCOSA POST-ERADICATION AND MAY ALLOW FOR THE DEVELOPMENT OF USEFUL BIOMARKERS.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
16  2938  21 GENETIC AND EPIGENETIC ALTERATIONS IN BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA. ESOPHAGEAL ADENOCARCINOMA (EAC) DEVELOPS FROM BARRETT'S ESOPHAGUS (BE), WHEREIN NORMAL SQUAMOUS EPITHELIA IS REPLACED BY SPECIALIZED INTESTINAL METAPLASIA IN RESPONSE TO CHRONIC GASTROESOPHAGEAL ACID REFLUX. BE CAN PROGRESS TO LOW- AND HIGH-GRADE DYSPLASIA, INTRAMUCOSAL, AND INVASIVE CARCINOMA. BOTH BE AND EAC ARE CHARACTERIZED BY LOSS OF HETEROZYGOSITY, ANEUPLOIDY, SPECIFIC GENETIC MUTATIONS, AND CLONAL DIVERSITY. GIVEN THE LIMITATIONS OF HISTOPATHOLOGY, GENOMIC AND EPIGENOMIC ANALYSES MAY IMPROVE THE PRECISION OF RISK STRATIFICATION. ASSAYS TO DETECT MOLECULAR ALTERATIONS ASSOCIATED WITH NEOPLASTIC PROGRESSION COULD BE USED TO IMPROVE THE PATHOLOGIC ASSESSMENT OF BE/EAC AND TO SELECT HIGH-RISK PATIENTS FOR MORE INTENSIVE SURVEILLANCE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
17  5180  23 PREMALIGNANT CONDITIONS OF GASTRIC CANCER. PREMALIGNANT LESIONS OF GASTRIC CANCER ENCOMPASS A VARIETY OF CONDITIONS SUCH AS CHRONIC GASTRITIS, INTESTINAL METAPLASIA AND DYSPLASIA, IN WHICH ELEVATED RISK OF DEVELOPING GASTRIC CANCER HAVE BEEN DOCUMENTED. AMONG THEM, INTESTINAL METAPLASIA IS FREQUENTLY ENCOUNTERED IN OUR DAILY ENDOSCOPIC EXAMINATION, YET ITS CLINICAL SIGNIFICANCE IS OFTEN UNDERESTIMATED DESPITE OF A NUMBER OF REPORTS DEMONSTRATING GENETIC AND EPIGENETIC ALTERATIONS IN THE INTESTINAL METAPLASTIC MUCOSA. IN THIS REVIEW, I WILL DESCRIBE THE MOLECULAR MECHANISMS OF PHENOTYPIC CHANGES FROM GASTRIC MUCOSA TO INTESTINAL METAPLASIA BASED ON OUR ANALYSIS OF MOUSE MODEL OF INTESTINAL METAPLASIA GENERATED BY ECTOPIC EXPRESSION OF CDX2 IN CONJUNCTION WITH THE STUDIES WITH HUMAN INTESTINAL METAPLASIA.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
18   414  32 ANALYSIS OF PROMOTER METHYLATION IN STOOL: A NOVEL METHOD FOR THE DETECTION OF COLORECTAL CANCER. BACKGROUND & AIMS: DETECTION OF TUMOR-DERIVED DNA ALTERATIONS IN STOOL IS AN INTRIGUING NEW APPROACH WITH HIGH POTENTIAL FOR THE NONINVASIVE DETECTION OF COLORECTAL CANCER (CRC). BECAUSE OF HETEROGENEITY OF TUMORS, USUALLY MULTIPLE MARKERS DISTRIBUTED THROUGHOUT THE HUMAN GENOME NEED TO BE ANALYZED. THIS IS LABOR INTENSIVE AND DOES NOT ALLOW FOR HIGH THROUGH-PUT SCREENING. THEREFORE, MARKERS WITH HIGH SENSITIVITY AND GOOD SPECIFICITY ARE NEEDED. WE EXPLORED THE POTENTIAL OF A SINGLE EPIGENETIC MARKER IN COMPARISON WITH FECAL OCCULT BLOOD TESTING (FOBT) FOR THE DISCRIMINATION OF PATIENTS WITH CRCS AND ADENOMAS FROM THOSE WITHOUT. METHODS: METHYLATION-SPECIFIC POLYMERASE CHAIN REACTION (PCR) WAS PERFORMED TO ANALYZE HYPERMETHYLATED IN CANCER 1 (HIC1) PROMOTER METHYLATION STATUS IN A BLINDED FASHION IN STOOL SAMPLES FROM 26 PATIENTS WITH CRC, 13 WITH ADENOMA > OR =1 CM, 9 WITH HYPERPLASTIC POLYPS, 9 WITH CHRONIC INFLAMMATORY BOWEL DISEASE, AND 32 WITH ENDOSCOPICALLY NORMAL COLON. RESULTS: NINETY-SEVEN PERCENT OF THE STOOL SAMPLES CONTAINED AMPLIFIABLE DNA. FORTY-TWO PERCENT OF THE SAMPLES FROM PATIENTS WITH CRC AND 31% OF THE SAMPLES FROM PATIENTS WITH COLORECTAL ADENOMA > OR =1 CM WERE POSITIVE FOR HIC1 PROMOTER METHYLATION. NO METHYLATED HIC1 PROMOTER DNA WAS DETECTED IN THE FECAL DNA FROM PATIENTS WITH ENDOSCOPICALLY NORMAL COLON OR HYPERPLASTIC POLYPS. CONCLUSIONS: THE EPIGENETIC MARKER HIC1 PROMOTER METHYLATION CARRIES HIGH POTENTIAL FOR THE REMOTE DETECTION OF CRCS. WE POSTULATE THAT A PANEL OF MERELY A FEW GENETIC AND EPIGENETIC MARKERS WILL BE REQUIRED FOR THE HIGHLY SENSITIVE AND SPECIFIC DETECTION OF CRCS AND ADENOMAS IN FECAL SAMPLES FROM AFFECTED PATIENTS.	2005	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
19  4725  30 NORMAL GASTRIC TISSUE HELICOBACTER PYLORI INFECTION IS ASSOCIATED WITH EPIGENETIC AGE ACCELERATION, INCREASED MITOTIC TICK RATE, TISSUE CELL COMPOSITION, AND NATURAL KILLER CELL METHYLATION ALTERATIONS. BACKGROUND: GASTRIC ADENOCARCINOMAS ARE A LEADING CAUSE OF GLOBAL MORTALITY, ASSOCIATED WITH CHRONIC INFECTION WITH HELICOBACTER PYLORI . THE MECHANISMS BY WHICH INFECTION WITH H. PYLORI CONTRIBUTES TO CARCINOGENESIS ARE NOT WELL UNDERSTOOD. RECENT STUDIES FROM SUBJECTS WITH AND WITHOUT GASTRIC CANCER HAVE IDENTIFIED SIGNIFICANT DNA METHYLATION ALTERATIONS IN NORMAL GASTRIC MUCOSA ASSOCIATED WITH H. PYLORI INFECTION AND GASTRIC CANCER RISK. HERE WE FURTHER INVESTIGATED DNA METHYLATION ALTERATIONS IN NORMAL GASTRIC MUCOSA IN GASTRIC CANCER CASES (N = 42) AND CONTROL SUBJECTS (N = 42) WITH H. PYLORI INFECTION DATA. WE ASSESSED TISSUE CELL TYPE COMPOSITION, DNA METHYLATION ALTERATIONS WITHIN CELL POPULATIONS, EPIGENETIC AGING, AND REPETITIVE ELEMENT METHYLATION. RESULTS: IN NORMAL GASTRIC MUCOSA OF BOTH GASTRIC CANCER CASES AND CONTROL SUBJECTS, WE OBSERVED INCREASED EPIGENETIC AGE ACCELERATION ASSOCIATED WITH H. PYLORI INFECTION. WE ALSO OBSERVED AN INCREASED MITOTIC TICK RATE ASSOCIATED WITH H. PYLORI INFECTION IN BOTH GASTRIC CANCER CASES AND CONTROLS. SIGNIFICANT DIFFERENCES IN IMMUNE CELL POPULATIONS ASSOCIATED WITH H. PYLORI INFECTION IN NORMAL TISSUE FROM CANCER CASES AND CONTROLS WERE IDENTIFIED USING DNA METHYLATION CELL TYPE DECONVOLUTION. WE ALSO FOUND NATURAL KILLER CELL-SPECIFIC METHYLATION ALTERATIONS IN NORMAL MUCOSA FROM GASTRIC CANCER PATIENTS WITH H. PYLORI INFECTION. CONCLUSIONS: OUR FINDINGS FROM NORMAL GASTRIC MUCOSA PROVIDE INSIGHT INTO UNDERLYING CELLULAR COMPOSITION AND EPIGENETIC ASPECTS OF H. PYLORI ASSOCIATED GASTRIC CANCER ETIOLOGY.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
20  5181  29 PREMALIGNANT LESIONS IN GASTRIC CANCER. DESPITE A PLATEAU IN INCIDENCE, GASTRIC CANCER IS ONE OF THE MOST COMMON CANCERS WORLDWIDE AND CAUSES CONSIDERABLE MORBIDITY AND MORTALITY. PREMALIGNANT GASTRIC LESIONS ARE WELL KNOWN RISK FACTORS FOR THE DEVELOPMENT OF INTESTINAL-TYPE GASTRIC ADENOCARCINOMAS. IN THIS MULTISTEP MODEL OF GASTRIC CARCINOGENESIS, HELICOBACTER PYLORI CAUSES CHRONIC ACTIVE INFLAMMATION OF THE GASTRIC MUCOSA, WHICH SLOWLY PROGRESSES THROUGH THE PREMALIGNANT STAGES OF ATROPHIC GASTRITIS, INTESTINAL METAPLASIA, AND ADENOMA/DYSPLASIA TO GASTRIC CARCINOMA. THIS PROGRESSION IS PARALLELED BY A STEPWISE ACCUMULATION OF MULTIPLE GENETIC AND EPIGENETIC ABNORMALITIES. DETECTION, TREATMENT, AND MOLECULAR ANALYSES OF PREMALIGNANT LESIONS MAY THUS PROVIDE A BASIS FOR GASTRIC CANCER PREVENTION. THIS REVIEW DESCRIBES AN OVERVIEW OF CURRENT KNOWLEDGE ON PREMALIGNANT GASTRIC LESIONS. IT ALSO REVIEWS THE ISSUE OF SURVEILLANCE OF PATIENTS WITH PREMALIGNANT LESIONS IN ORDER TO IMPROVE THE SURVIVAL OF PATIENTS WITH GASTRIC CANCER.	2010