1 4316 116 MICRORNAS AS NON-INVASIVE DIAGNOSTIC BIOMARKERS FOR GASTRIC CANCER: CURRENT INSIGHTS AND FUTURE PERSPECTIVES. NON-INVASIVE DIAGNOSTIC BIOMARKERS MAY CONTRIBUTE TO AN EARLY IDENTIFICATION OF GASTRIC CANCER (GC) AND IMPROVE THE CLINICAL MANAGEMENT. UNFORTUNATELY, NO SENSITIVE AND SPECIFIC SCREENING BIOMARKERS ARE AVAILABLE YET AND THE CURRENTLY AVAILABLE APPROACHES ARE LIMITED BY THE NATURE OF THE DISEASE. GC IS A HETEROGENIC DISEASE WITH VARIOUS DISTINCT GENETIC AND EPIGENETIC EVENTS THAT OCCUR DURING THE MULTIFACTORIAL CASCADE OF CARCINOGENESIS. MICRORNAS (MIRNAS) ARE COMMONLY DEREGULATED IN GASTRIC MUCOSA DURING THE HELICOBACTER PYLORI INFECTION AND IN STEPWISE MANNER FROM CHRONIC GASTRITIS, THROUGH PRENEOPLASTIC CONDITIONS SUCH AS ATROPHIC GASTRITIS AND INTESTINAL METAPLASIA, TO EARLY DYSPLASIA AND INVASIVE CANCER. IDENTIFICATION OF MIRNAS IN BLOOD IN 2008 LED TO A GREAT INTEREST ON MIRNA-BASED DIAGNOSTIC, PROGNOSTIC BIOMARKERS IN GC. IN THIS REVIEW, WE PROVIDE THE MOST RECENT SYSTEMATIC REVIEW ON THE EXISTING STUDIES RELATED TO MIRNAS AS DIAGNOSTIC BIOMARKERS FOR GC. HERE, WE SYSTEMATICALLY EVALUATE 75 STUDIES RELATED TO DIFFERENTIAL EXPRESSION OF CIRCULATING MIRNAS IN GC PATIENTS AND PROVIDE NOVEL VIEW ON VARIOUS HETEROGENIC ASPECTS OF THE EXISTING DATA AND SUMMARIZE THE METHODOLOGICAL DIFFERENCES. FINALLY, WE HIGHLIGHT SEVERAL IMPORTANT ASPECTS CRUCIAL TO IMPROVE THE FUTURE TRANSLATIONAL AND CLINICAL RESEARCH IN THE FIELD. 2018 2 4733 35 NOVEL BIOMARKERS FOR THE IDENTIFICATION AND TARGETED THERAPY OF GASTRIC CANCER. GASTRIC CANCER DEVELOPMENT FOLLOWS THE PATHOLOGIC PATTERN SUCH THAT CHRONIC INFLAMMATION IN THE GASTRIC MUCOSA PROGRESSIVELY TRANSFORMS NORMAL MUCOSA INTO ATROPHY, INTESTINAL METAPLASIA, ADENOMA/DYSPLASIA AND EVENTUALLY INVASIVE AND METASTATIC TUMORS. THE ACCUMULATION OF MULTIPLE GENETIC AND EPIGENETIC ALTERATIONS LEADS TO THE DYSREGULATION OF ONCOGENES AND TUMOR SUPPRESSORS, WHICH WAS CONSIDERED AS THE DRIVER BEHIND EVENTS DURING THE TUMORIGENESIS. ALMOST ALL GASTRIC CANCERS ARE ADENOCARCINOMAS, WHICH SHARE CONSIDERABLE HETEROGENEITY WITH DISTINCT MORPHOLOGY, PATHOGENESIS AND CLINICAL BEHAVIOR. THEREFORE, IDENTIFYING SUBTYPES OF GASTRIC CANCERS WITH MOLECULAR AND GENETIC FEATURES WILL BE BENEFICIAL FOR THE EARLY IDENTIFICATION AND SELECTION OF NEW EFFECTIVE AGENTS FOR TARGETED TREATMENT. HIGH-THROUGHPUT SEQUENCING TECHNIQUES SUCH AS WHOLE GENOMIC, EPIGENOME AND TRANSCRIPTOME SEQUENCING AND PROTEOMICS PLATFORMS HAVE IDENTIFIED MAJOR GENOMIC CHARACTERISTICS THAT EXHIBIT IDENTIFICATION AND PROGNOSTIC IMPACTS AND DISTINCT RESPONSE PATTERNS. IN THIS ARTICLE, THE AUTHORS AIM TO SUMMARIZE THE INFORMATION REGARDING THE MOST PROMISING MOLECULES THAT MAY HAVE CLINICAL APPLICATION AS NON-INVASIVE BIOMARKERS AND THERAPY TARGETS. 2015 3 3849 34 IS ERADICATION OF HELICOBACTER PYLORI THE FEASIBLE WAY TO PREVENT GASTRIC CANCER? NEW EVIDENCE AND PROGRESS, BUT STILL A LONG WAY TO GO. EPIDEMIOLOGICAL, ANIMAL AND BIOLOGICAL STUDIES PROVIDE COMPELLING EVIDENCE FOR THE ROLE OF HELICOBACTER PYLORI INFECTION IN GASTRIC CARCINOGENESIS. THE FINDING THAT H. PYLORI-INDUCED CHRONIC ATROPHIC GASTRITIS IS THE MAJOR CAUSE OF GASTRIC CANCER SUGGESTS THAT ERADICATION OF THE BACTERIUM MAY PREVENT THIS MALIGNANCY. COMPUTER-SIMULATION STUDIES HAVE CONFIRMED THE COST-EFFECTIVENESS OF ERADICATION IN HIGH-RISK SUBJECTS; HOWEVER, UNRESOLVED ISSUES COMPLICATE ACTIVE TESTING FOR AND TREATMENT OF H. PYLORI INFECTION AMONG ASYMPTOMATIC CARRIERS. CONCERNS INCLUDE THE ENORMOUS COSTS FOR DEVELOPING COUNTRIES TO IMPLEMENT STRATEGIES, THE INCONCLUSIVENESS OF DATA FROM RANDOMIZED CONTROLLED STUDIES, THE POTENTIAL INDUCTION OF ANTIMICROBIAL RESISTANCE, AND THE UNCERTAIN EFFECT OF ELIMINATING THIS ORGANISM ON THE SPECTRUM OF MODERN DISEASE. ALTHOUGH CURRENT EVIDENCE IS INSUFFICIENT TO RECOMMEND UNIVERSAL TESTING AND TREATMENT, IT IS POSSIBLE TO IDENTIFY HIGHLY SUSCEPTIBLE INDIVIDUALS WHO ARE MOST LIKELY TO BENEFIT FROM TREATMENT. NOVEL BIOMARKERS FOR PREDICTING RISK ARE UNDER EXTENSIVE INVESTIGATION, INCLUDING GENETIC, EPIGENETIC AND PROTEINOMIC FACTORS. THE EMERGING EVIDENCE SUGGESTS THAT TREATMENT OF H. PYLORI INFECTION IN ASYMPTOMATIC CARRIERS MAY DECREASE THE BURDEN OF GASTRIC CANCER. HOWEVER, CONFIRMATION OF LONG-TERM BENEFITS REMAINS A LONG WAY OFF. 2008 4 1522 38 DNA METHYLATION CHANGE PROFILING OF COLORECTAL DISEASE: SCREENING TOWARDS CLINICAL USE. COLON CANCER REMAINS ONE OF THE LEADING CAUSES OF CANCER-RELATED DEATHS WORLDWIDE. TRANSFORMATION OF COLON EPITHELIAL CELLS INTO INVASIVE ADENOCARCINOMAS HAS BEEN WELL KNOWN TO BE DUE TO THE ACCUMULATION OF MULTIPLE GENETIC AND EPIGENETIC CHANGES. IN THE PAST DECADE, THE ETIOLOGY OF INFLAMMATORY BOWEL DISEASE (IBD) WHICH IS CHARACTERIZED BY CHRONIC INFLAMMATION OF THE INTESTINAL MUCOSA, WAS ONLY PARTIALLY EXPLAINED BY GENETIC STUDIES PROVIDING SUSCEPTIBILITY LOCI, BUT RECENTLY EPIGENETIC STUDIES HAVE PROVIDED CRITICAL EVIDENCES AFFECTING IBD PATHOGENESIS. OVER THE PAST DECADE, A DEEP UNDERSTANDING OF EPIGENETICS ALONG WITH TECHNOLOGICAL ADVANCES HAVE LED TO IDENTIFYING NUMEROUS GENES THAT ARE REGULATED BY PROMOTER DNA HYPERMETHYLATION IN COLORECTAL DISEASES. RECENT ADVANCES IN OUR UNDERSTANDING OF THE ROLE OF DNA METHYLATION IN COLORECTAL DISEASES COULD IMPROVE A MULTITUDE OF POWERFUL DNA METHYLATION-BASED BIOMARKERS, PARTICULARLY FOR USE AS DIAGNOSIS, PROGNOSIS, AND PREDICTION FOR THERAPEUTIC APPROACHES. THIS REVIEW FOCUSES ON THE EMERGING POTENTIAL FOR TRANSLATIONAL RESEARCH OF EPIGENETIC ALTERATIONS INTO CLINICAL UTILITY AS MOLECULAR BIOMARKERS. MOREOVER, THIS REVIEW DISCUSSES RECENT PROGRESS REGARDING THE IDENTIFICATION OF UNKNOWN HYPERMETHYLATED GENES IN COLON CANCERS AND IBD, AS WELL AS THEIR POSSIBLE ROLE IN CLINICAL PRACTICE, WHICH WILL HAVE IMPORTANT CLINICAL SIGNIFICANCE, PARTICULARLY IN THE ERA OF THE PERSONALIZED MEDICINE. 2021 5 4429 34 MOLECULAR BIOLOGY AS A TOOL FOR THE TREATMENT OF CANCER. CANCER IS A GENETIC DISEASE CHARACTERIZED BY UNCONTROLLED CELL GROWTH AND METASTASIS. CANCER CAN HAVE A NUMBER OF CAUSES, SUCH THE ACTIVATION OF ONCOGENES, THE INACTIVATION OF TUMOR-SUPPRESSING GENES, MUTAGENESIS PROVOKED BY EXTERNAL FACTORS, AND EPIGENETIC MODIFICATIONS. THE DEVELOPMENT OF DIAGNOSTIC TOOLS AND TREATMENTS USING A MOLECULAR BIOLOGICAL APPROACH PERMITS THE USE OF SENSITIVE, LOW-COST, NONINVASIVE TESTS FOR CANCER PATIENTS. BIOMARKERS CAN BE USED TO PROVIDE RAPID, PERSONALIZED ONCOLOGY, IN PARTICULAR THE MOLECULAR DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA, AND GASTRIC, COLON, AND BREAST CANCERS. MOLECULAR TESTS BASED ON DNA METHYLATION CAN ALSO BE USED TO DIRECT TREATMENTS OR EVALUATE THE TOXIC EFFECTS OF CHEMOTHERAPY. THE ADEQUATE DIAGNOSIS, PROGNOSIS, AND PREDICTION OF THE RESPONSE OF CANCER PATIENTS TO TREATMENT ARE ESSENTIAL TO ENSURE THE MOST EFFECTIVE THERAPY, REDUCE THE DAMAGING EFFECTS OF TREATMENT, AND DIRECT THE THERAPY TO SPECIFIC TARGETS, AND IN THIS CONTEXT, MOLECULAR BIOLOGY HAS BECOME INCREASINGLY IMPORTANT IN ONCOLOGY. IN THIS BRIEF REVIEW, WE WILL DEMONSTRATE THE FUNDAMENTAL IMPORTANCE OF MOLECULAR BIOLOGY FOR THE TREATMENT OF THREE TYPES OF CANCER-CHRONIC MYELOID LEUKEMIA, HEREDITARY DIFFUSE GASTRIC CANCER, AND ASTROCYTOMAS (SPORADIC TUMORS OF THE CENTRAL NERVOUS SYSTEM). IN EACH OF THESE THREE MODELS, DISTINCT BIOLOGICAL MECHANISMS ARE INVOLVED IN THE TRANSFORMATION OF THE CELLS, BUT IN ALL CASES, MOLECULAR BIOLOGY IS FUNDAMENTAL TO THE DEVELOPMENT OF PERSONALIZED ANALYSES FOR EACH PATIENT AND EACH TYPE OF NEOPLASIA, AND TO GUARANTEE THE SUCCESS OF THE TREATMENT. 2018 6 3958 38 LONG NON-CODING RNAS IN BONE METASTASIS: PROGRESSES AND PERSPECTIVES AS POTENTIAL DIAGNOSTIC AND PROGNOSTIC BIOMARKERS. IN A PRECISION MEDICINE PERSPECTIVE, AMONG THE BIOMARKERS POTENTIALLY USEFUL FOR EARLY DIAGNOSIS OF CANCERS, AS WELL AS TO DEFINE THEIR PROGNOSIS AND EVENTUALLY TO IDENTIFY NOVEL AND MORE EFFECTIVE THERAPEUTIC TARGETS, THERE ARE THE LONG NON-CODING RNAS (LNCRNAS). THE TERM LNCRNA IDENTIFIES A CLASS OF NON-CODING RNA MOLECULES INVOLVED IN THE REGULATION OF GENE EXPRESSION THAT INTERVENE AT THE TRANSCRIPTIONAL, POST-TRANSCRIPTIONAL, AND EPIGENETIC LEVEL. METASTASIS IS A NATURAL EVOLUTION OF SOME MALIGNANT TUMOURS, FREQUENTLY ENCOUNTERED IN PATIENTS WITH ADVANCED CANCERS. ONSET AND DEVELOPMENT OF METASTASIS REPRESENTS A DETRIMENTAL EVENT THAT WORSEN THE PATIENT'S PROGNOSIS BY PROFOUNDLY INFLUENCING THE QUALITY OF LIFE AND IS RESPONSIBLE FOR THE OMINOUS PROGRESSION OF THE DISEASE. DUE TO THE PECULIAR ENVIRONMENT AND THE BIOMECHANICAL PROPERTIES, BONE IS A PREFERENTIAL SITE FOR THE SECONDARY GROWTH OF BREAST, PROSTATE AND LUNG CANCERS. UNFORTUNATELY, ONLY PALLIATIVE AND PAIN THERAPIES ARE CURRENTLY AVAILABLE FOR PATIENTS WITH BONE METASTASES, WHILE NO EFFECTIVE AND DEFINITIVE TREATMENTS ARE AVAILABLE. THE UNDERSTANDING OF PATHOPHYSIOLOGICAL BASIS OF BONE METASTASIS FORMATION AND PROGRESSION, AS WELL AS THE IMPROVEMENT IN THE CLINICAL MANAGEMENT OF THE PATIENT, ARE CENTRAL BUT CHALLENGING TOPICS IN BASIC RESEARCH AND CLINICAL PRACTICE. THE IDENTIFICATION OF NEW MOLECULAR SPECIES THAT MAY HAVE A ROLE AS EARLY HALLMARKS OF THE METASTATIC PROCESS COULD OPEN THE DOOR TO THE DEFINITION OF NEW, AND MORE EFFECTIVE, THERAPEUTIC AND DIAGNOSTIC APPROACHES. NON-CODING RNAS SPECIES AND, PARTICULARLY, LNCRNAS ARE PROMISING COMPOUNDS IN THIS SETTING, AND THEIR STUDY MAY BRING TO THE IDENTIFICATION OF RELEVANT PROCESSES. IN THIS REVIEW, WE HIGHLIGHT THE ROLE OF LNCRNAS AS EMERGING MOLECULES IN MEDIATING THE FORMATION AND DEVELOPMENT OF BONE METASTASES, AS POSSIBLE BIOMARKERS FOR CANCER DIAGNOSIS AND PROGNOSIS, AND AS THERAPEUTIC TARGETS TO COUNTERACT CANCER SPREAD. 2023 7 1958 31 EPIGENETIC AGING AND COLORECTAL CANCER: STATE OF THE ART AND PERSPECTIVES FOR FUTURE RESEARCH. ALTHOUGH TRANSLATIONAL RESEARCH HAS IDENTIFIED A LARGE NUMBER OF POTENTIAL BIOMARKERS INVOLVED IN COLORECTAL CANCER (CRC) CARCINOGENESIS, A BETTER UNDERSTANDING OF THE MOLECULAR PATHWAYS ASSOCIATED WITH BIOLOGICAL AGING IN COLORECTAL CELLS AND TISSUES IS NEEDED. HERE, WE AIM TO SUMMARIZE THE STATE OF THE ART ABOUT THE ROLE OF AGE ACCELERATION, DEFINED AS THE DIFFERENCE BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE, IN THE DEVELOPMENT AND PROGRESSION OF CRC. SOME STUDIES HAVE SHOWN THAT ACCELERATED BIOLOGICAL AGING IS POSITIVELY ASSOCIATED WITH THE RISK OF CANCER AND DEATH IN GENERAL. IN LINE WITH THESE FINDINGS, OTHER STUDIES HAVE SHOWN HOW THE ASSESSMENT OF EPIGENETIC AGE IN PEOPLE AT RISK FOR CRC COULD BE HELPFUL FOR MONITORING THE MOLECULAR RESPONSE TO PREVENTIVE INTERVENTIONS. MOREOVER, IT WOULD BE INTERESTING TO INVESTIGATE WHETHER ABERRANT EPIGENETIC AGING COULD HELP IDENTIFY CRC PATIENTS WITH A HIGH RISK OF RECURRENCE AND A WORST PROGNOSIS, AS WELL AS THOSE WHO RESPOND POORLY TO TREATMENT. YET, THE APPLICATION OF THIS NOVEL CONCEPT IS STILL IN ITS INFANCY, AND FURTHER RESEARCH SHOULD BE ENCOURAGED IN ANTICIPATION OF FUTURE APPLICATIONS IN CLINICAL PRACTICE. 2020 8 3964 35 LONG NONCODING RNAS IN LUNG CANCER. DESPITE GREAT PROGRESS IN RESEARCH AND TREATMENT OPTIONS, LUNG CANCER REMAINS THE LEADING CAUSE OF CANCER-RELATED DEATHS WORLDWIDE. ONCOGENIC DRIVER MUTATIONS IN PROTEIN-ENCODING GENES WERE DEFINED AND ALLOW FOR PERSONALIZED THERAPIES BASED ON GENETIC DIAGNOSES. NONETHELESS, DIAGNOSIS OF LUNG CANCER MOSTLY OCCURS AT LATE STAGES, AND CHRONIC TREATMENT IS FOLLOWED BY A FAST ONSET OF CHEMORESISTANCE. HENCE, THERE IS AN URGENT NEED FOR RELIABLE BIOMARKERS AND ALTERNATIVE TREATMENT OPTIONS. WITH THE ERA OF WHOLE GENOME AND TRANSCRIPTOME SEQUENCING TECHNOLOGIES, LONG NONCODING RNAS EMERGED AS A NOVEL CLASS OF VERSATILE, FUNCTIONAL RNA MOLECULES. ALTHOUGH FOR MOST OF THEM THE MECHANISM OF ACTION REMAINS TO BE DEFINED, ACCUMULATING EVIDENCE CONFIRMS THEIR INVOLVEMENT IN VARIOUS ASPECTS OF LUNG TUMORIGENESIS. THEY ARE FUNCTIONAL ON THE EPIGENETIC, TRANSCRIPTIONAL, AND POSTTRANSCRIPTIONAL LEVEL AND ARE REGULATORS OF PATHOPHYSIOLOGICAL KEY PATHWAYS INCLUDING CELL GROWTH, APOPTOSIS, AND METASTASIS. LONG NONCODING RNAS ARE GAINING INCREASING ATTENTION AS POTENTIAL BIOMARKERS AND A NOVEL CLASS OF DRUGGABLE MOLECULES. IT HAS BECOME CLEAR THAT WE ARE ONLY BEGINNING TO UNDERSTAND THE COMPLEXITY OF TUMORIGENIC PROCESSES. THE CLINICAL INTEGRATION OF LONG NONCODING RNAS IN TERMS OF PROGNOSTIC AND PREDICTIVE BIOMARKER SIGNATURES AND ADDITIONAL CANCER TARGETS COULD PROVIDE A CHANCE TO INCREASE THE THERAPEUTIC BENEFIT. HERE, WE REVIEW THE CURRENT KNOWLEDGE ABOUT THE EXPRESSION, REGULATION, BIOLOGICAL FUNCTION, AND CLINICAL RELEVANCE OF LONG NONCODING RNAS IN LUNG CANCER. 2016 9 2975 28 GENETIC AND MOLECULAR ALTERATIONS ASSOCIATED WITH ORAL SQUAMOUS CELL CANCER (REVIEW). THE DEVELOPMENT OF ORAL SQUAMOUS CELL CANCER (OSCC) IS A MULTISTEP PROCESS INVOLVING THE ACCUMULATION OF MULTIPLE GENETIC ALTERATIONS MODULATED BY GENETIC PRE-DISPOSITION AND ENVIRONMENTAL INFLUENCES SUCH AS TOBACCO AND ALCOHOL USE, CHRONIC INFLAMMATION, AND VIRAL INFECTIONS. ALL OF THESE FACTORS CAN LEAD TO A WIDE RANGE OF GENETIC AND MOLECULAR ALTERATIONS THAT CAN BE DETECTED USING A RANGE OF MOLECULAR STUDIES. THE ALTERATIONS MOSTLY AFFECT TWO LARGE GROUPS OF GENES: ONCOGENES AND TUMOR SUPPRESSOR GENES, WHICH CAN BE EITHER INACTIVATED OR OVEREXPRESSED THROUGH MUTATIONS, LOSS OF HETEROZYGOSITY, DELETIONS, OR EPIGENETIC MODIFICATIONS SUCH AS METHYLATION. OTHER MOLECULES THAT ARE CLOSELY ASSOCIATED WITH TUMOR PATHOGENESIS AND PROGNOSIS ALSO EXIST AND WARRANT FURTHER STUDY. IMPORTANT ADVANCES IN MOLECULAR BIOLOGY ARE HELPING TO SHED LIGHT ON ORAL CANCER AND THUS AIDING IN THE EARLY DIAGNOSIS AND DEVELOPMENT OF NEW PERSONALIZED TREATMENT APPROACHES. THE PURPOSE OF THE REVIEW IS TO EXPLORE THE GENETIC AND MOLECULAR ALTERATIONS ASSOCIATED WITH OSCC. 2009 10 3220 42 HELICOBACTER PYLORI AND MICRORNAS: RELATION WITH INNATE IMMUNITY AND PROGRESSION OF PRENEOPLASTIC CONDITIONS. THE ACCEPTED PARADIGM FOR INTESTINAL-TYPE GASTRIC CANCER PATHOGENESIS IS A MULTISTEP PROGRESSION FROM CHRONIC GASTRITIS INDUCED BY HELICOBACTER PYLORI (H. PYLORI) TO GASTRIC ATROPHY, INTESTINAL METAPLASIA, DYSPLASIA AND ULTIMATELY GASTRIC CANCER. THE GENETIC AND MOLECULAR MECHANISMS UNDERLYING DISEASE PROGRESSION ARE STILL NOT COMPLETELY UNDERSTOOD AS ONLY A FRACTION OF COLONIZED INDIVIDUALS EVER DEVELOP NEOPLASIA SUGGESTING THAT BACTERIAL, HOST AND ENVIRONMENTAL FACTORS ARE INVOLVED. MICRORNAS ARE NONCODING RNAS THAT MAY INFLUENCE H. PYLORI-RELATED PATHOLOGY THROUGH THE REGULATION OF THE TRANSCRIPTION AND EXPRESSION OF VARIOUS GENES, PLAYING AN IMPORTANT ROLE IN INFLAMMATION, CELL PROLIFERATION, APOPTOSIS AND DIFFERENTIATION. INDEED, H. PYLORI HAVE BEEN SHOWN TO MODIFY MICRORNA EXPRESSION IN THE GASTRIC MUCOSA AND MICRORNAS ARE INVOLVED IN THE IMMUNE HOST RESPONSE TO THE BACTERIA AND IN THE REGULATION OF THE INFLAMMATORY RESPONSE. MICRORNAS HAVE A KEY ROLE IN THE REGULATION OF INFLAMMATORY PATHWAYS AND H. PYLORI MAY INFLUENCE INFLAMMATION-MEDIATED GASTRIC CARCINOGENESIS POSSIBLY THROUGH DNA METHYLATION AND EPIGENETIC SILENCING OF TUMOR SUPPRESSOR MICRORNAS. FURTHERMORE, MICRORNAS INFLUENCED BY H. PYLORI ALSO HAVE BEEN FOUND TO BE INVOLVED IN CELL CYCLE REGULATION, APOPTOSIS AND EPITHELIAL-MESENCHYMAL TRANSITION. ALTOGETHER, MICRORNAS SEEM TO HAVE AN IMPORTANT ROLE IN THE PROGRESSION FROM GASTRITIS TO PRENEOPLASTIC CONDITIONS AND NEOPLASTIC LESIONS AND SINCE EACH MICRORNA CAN CONTROL THE EXPRESSION OF HUNDREDS TO THOUSANDS OF GENES, KNOWLEDGE OF MICRORNAS TARGET GENES AND THEIR FUNCTIONS ARE OF PARAMOUNT IMPORTANCE. IN THIS ARTICLE WE PRESENT A COMPREHENSIVE REVIEW ABOUT THE ROLE OF MICRORNAS IN H. PYLORI GASTRIC CARCINOGENESIS, IDENTIFYING THE MICRORNAS DOWNREGULATED AND UPREGULATED IN THE INFECTION AND CLARIFYING THEIR BIOLOGICAL ROLE IN THE LINK BETWEEN IMMUNE HOST RESPONSE, INFLAMMATION, DNA METHYLATION AND GASTRIC CARCINOGENESIS. 2015 11 3697 27 INFLAMMATORY MARKERS IN CANCER: POTENTIAL RESOURCES. CANCER IS A LEADING CAUSE OF DEATH WORLDWIDE AND A MAJOR BURDEN ON DEVELOPING AND LESS DEVELOPED COUNTRIES OF THE WORLD WITH LIMITED RESOURCES FOR PREVENTION AND EFFECTIVE TREATMENT OF CANCER. ALTHOUGH CANCER IS MULTIFACTORIAL IN ORIGIN, VARIOUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST THAT CHRONIC INFLAMMATION HAS AN IMPORTANT ROLE IN ALL STAGES OF CANCER, FROM INITIATION TO PROGRESSION AND EVEN SURVIVAL OF THE PATIENT. INFLAMMATORY PRODUCTS LIKE CYTOKINES, CHEMOKINES, LEUCOCYTES, PROSTAGLANDINS, CYCLOOXYGENASE, REACTIVE OXYGEN AND NITROGEN SPECIES, METALLOPROTEINASE INDUCE GENETIC AND EPIGENETIC CHANGES IN NORMAL CELLS DAMAGING ITS DNA, INHIBITING ITS REPAIR, ALTERING TRANSCRIPTION FACTORS, PREVENTING APOPTOSIS, AND STIMULATING ANGIOGENESIS, AND THUS RESULTING IN CARCINOGENESIS. THUS, THESE INFLAMMATORY MEDIATORS HAVE A POTENTIAL ROLE TO BECOME CANCER BIOMARKERS FOR ALL STAGES OF CANCER AS MANY OF THEM CAN BE MEASURED IN A COST-EFFECTIVE MANNER. HOWEVER, LARGE SCALE PROSPECTIVE TRIALS ARE REQUIRED TO VALIDATE THESE POTENTIAL CANCER BIOMARKERS. NONETHELESS, A TRANSITION FROM POTENTIAL TO PRACTICAL UTILIZATION OF THESE MARKERS WILL BE AN EFFECTIVE TOOL FOR THE AMELIORATION OF CANCER BURDEN AND MORTALITY IN A RESOURCE LIMITED SETTING. 2020 12 2122 32 EPIGENETIC IMPACT OF INFECTION ON CARCINOGENESIS: MECHANISMS AND APPLICATIONS. VIRAL AND BACTERIAL INFECTIONS ARE INVOLVED IN THE DEVELOPMENT OF HUMAN CANCERS, SUCH AS LIVER, NASOPHARYNGEAL, CERVICAL, HEAD AND NECK, AND GASTRIC CANCERS. ABERRANT DNA METHYLATION IS FREQUENTLY PRESENT IN THESE CANCERS, AND SOME OF THE ABERRANTLY METHYLATED GENES ARE CAUSALLY INVOLVED IN CANCER DEVELOPMENT AND PROGRESSION. NOTABLY, ABERRANT DNA METHYLATION CAN BE PRESENT EVEN IN NON-CANCEROUS OR PRECANCEROUS TISSUES, AND ITS LEVELS CORRELATE WITH THE RISK OF CANCER DEVELOPMENT, PRODUCING A SO-CALLED 'EPIGENETIC FIELD FOR CANCERIZATION'. MECHANISTICALLY, MOST VIRAL OR BACTERIAL INFECTIONS INDUCE DNA METHYLATION INDIRECTLY VIA CHRONIC INFLAMMATION, BUT RECENT STUDIES HAVE INDICATED THAT SOME VIRUSES HAVE DIRECT EFFECTS ON THE EPIGENETIC MACHINERY OF HOST CELLS. FROM A TRANSLATIONAL VIEWPOINT, A RECENT MULTICENTER PROSPECTIVE COHORT STUDY DEMONSTRATED THAT ASSESSMENT OF THE EXTENT OF ALTERATIONS IN DNA METHYLATION IN NON-CANCEROUS TISSUES CAN BE USED TO PREDICT CANCER RISK. FURTHERMORE, SUPPRESSION OF ABERRANT DNA METHYLATION WAS SHOWN TO BE A USEFUL STRATEGY FOR CANCER PREVENTION IN AN ANIMAL MODEL. HERE, WE REVIEW THE INVOLVEMENT OF ABERRANT DNA METHYLATION IN VARIOUS TYPES OF INFECTION-ASSOCIATED CANCERS, ALONG WITH INDIVIDUAL INDUCTION MECHANISMS, AND WE DISCUSS THE APPLICATION OF THESE FINDINGS FOR CANCER PREVENTION, DIAGNOSIS, AND THERAPY. 2016 13 1799 32 EFFECT OF HELICOBACTER PYLORI INFECTION ON THE COMPOSITION OF GASTRIC MICROBIOTA IN THE DEVELOPMENT OF GASTRIC CANCER. BACKGROUND: GASTRIC CANCER IS ONE OF THE MOST COMMON CANCER TYPES WORLDWIDE. IN CHINA, GASTRIC CANCER HAS BECOME ONE OF THE MAJOR THREATS FOR PUBLIC HEALTH, RANKING SECOND ON INCIDENCE AND THIRD ON CAUSE OF CANCER DEATH. DESPITE THE COMMON RISK FACTORS THAT PROMOTE THE DEVELOPMENT OF GASTRIC CANCER, THE HUGE QUANTITY OF MICROORGANISM COLONIES WITHIN THE GASTROINTESTINAL TRACT, PARTICULARLY HELICOBACTER PYLORI INFECTION, DEMONSTRATES A CORRELATION WITH CHRONIC INFLAMMATION AND GASTRIC CARCINOGENESIS, AS EPIDEMIOLOGICAL STUDIES HAVE DETERMINED THAT H. PYLORI INFECTION CONFERS APPROXIMATELY 75% OF THE ATTRIBUTABLE RISK FOR GASTRIC CANCER. SUMMARY: THE CURRENT ARTICLE DRAWS AN OVERVIEW ON THE CORRELATION BETWEEN THE MICROBIOTA, INFLAMMATION AND GASTRIC TUMORIGENESIS. H. PYLORI INFECTION HAS BEEN IDENTIFIED AS THE MAIN RISK FACTOR AS IT TRIGGERS EPITHELIAL BARRIER DISRUPTION, SURVIVAL SIGNALING AS WELL AS GENETIC/EPIGENETIC MODULATION. APART FROM H. PYLORI, THE EXISTENCE OF A DIVERSE AND COMPLEX COMPOSITION OF MICROBIOTA IN THE STOMACH HAS BEEN IDENTIFIED, WHICH SUPPORTS A ROLE OF MICROBIOTA IN THE DEVELOPMENT OF GASTRIC CANCER. MOREOVER, METAGENOMICS STUDIES FOCUSED ON THE COMPOSITION AND FUNCTION OF THE MICROBIOTA HAVE ASSOCIATED MICROBIOTA WITH GASTRIC METABOLIC DISEASES AND EVEN TUMORIGENESIS. APART FROM THE GASTRIC MICROBIOTA, INFLAMMATION IS ANOTHER IDENTIFIED CONTRIBUTOR TO CANCER DEVELOPMENT AS WELL. KEY MESSAGE: THOUGH H. PYLORI INFECTION AND THE NON-H. PYLORI MICROBIOTA PLAY A ROLE IN GASTRIC CANCER, THE PROPERTIES OF GASTRIC MICROBIOTA AND MECHANISMS BY WHICH THEY PARTICIPATE IN THE GENESIS OF GASTRIC CANCER ARE STILL NOT CLEARLY DEPICTED. MOREOVER, IT REMAINS TO BE UNDERSTOOD HOW THE PRESENCE OF MICROBIOTA ALONG WITH H. PYLORI INFECTION AFFECTS THE PROGRESS FROM GASTRIC DISEASE TO CANCER. PRACTICAL IMPLICATIONS: THIS ARTICLE SUMMARIZED A CLUE OF THE CURRENT STUDIES ON MICROBIOTA, H. PYLORI INFECTION AND THE PROGRESSION FROM GASTRIC DISEASE TO CANCER. 2015 14 5742 26 SMOKING MOLECULAR DAMAGE IN BRONCHIAL EPITHELIUM. OUR UNDERSTANDING OF THE MOLECULAR PATHOLOGY OF LUNG CANCER IS ADVANCING RAPIDLY WITH SEVERAL SPECIFIC GENES AND CHROMOSOMAL REGIONS BEING IDENTIFIED. LUNG CANCER APPEARS TO REQUIRE MANY MUTATIONS IN BOTH DOMINANT AND RECESSIVE ONCOGENES TO POSSESS MALIGNANT PHENOTYPES. SEVERAL GENETIC AND EPIGENETIC CHANGES ARE COMMON TO ALL LUNG CANCER HISTOLOGIC TYPES, WHILE OTHERS APPEAR TO BE CELL TYPE SPECIFIC. HOWEVER, SPECIFIC ROLES OF THE GENES UNDERGOING MUTATIONS AND THE ORDER OF CUMULATIVE MOLECULAR CHANGES THAT LEAD TO THE DEVELOPMENT OF EACH LUNG TUMOR HISTOLOGIC TYPE REMAIN TO BE FULLY ELUCIDATED. RECENT FINDINGS OF MOLECULAR ABNORMALITIES IN NORMAL APPEARING AND PRENEOPLASTIC BRONCHIAL EPITHELIUM FROM PATIENTS WITH LUNG CANCER AND CHRONIC SMOKERS SUGGEST THAT GENETIC CHANGES MAY SERVE AS BIOMARKERS FOR EARLY DIAGNOSIS, RISK ASSESSMENT AND MONITORING RESPONSE TO CHEMOPREVENTION. 2002 15 186 25 ACCUMULATION OF GENETIC AND EPIGENETIC ALTERATIONS IN NORMAL CELLS AND CANCER RISK. CANCERS DEVELOP DUE TO THE ACCUMULATION OF GENETIC AND EPIGENETIC ALTERATIONS. GENETIC ALTERATIONS ARE INDUCED BY AGING, MUTAGENIC CHEMICALS, ULTRAVIOLET LIGHT, AND OTHER FACTORS; WHEREAS, EPIGENETIC ALTERATIONS ARE MAINLY BY AGING AND CHRONIC INFLAMMATION. THE ACCUMULATION AND PATTERNS OF ALTERATIONS IN NORMAL CELLS REFLECT OUR PAST EXPOSURE LEVELS AND LIFE HISTORY. MOST ACCUMULATED ALTERATIONS ARE CONSIDERED AS PASSENGERS, BUT THEIR ACCUMULATION IS CORRELATED WITH CANCER DRIVERS. THIS HAS BEEN SHOWN FOR ABERRANT DNA METHYLATION BUT HAS ONLY BEEN SPECULATED FOR GENETIC ALTERATIONS. HOWEVER, RECENT TECHNOLOGICAL ADVANCEMENTS HAVE ENABLED MEASUREMENT OF RARE POINT MUTATIONS, AND STUDIES HAVE SHOWN THAT THEIR ACCUMULATION LEVELS ARE INDEED CORRELATED WITH CANCER RISK. WHEN THE ACCUMULATION LEVELS OF ABERRANT DNA METHYLATION AND POINT MUTATIONS ARE COMBINED, RISK PREDICTION BECOMES EVEN MORE ACCURATE. WHEN HIGH LEVELS OF ALTERATIONS ACCUMULATE, THE TISSUE HAS A HIGH RISK OF DEVELOPING CANCER OR EVEN MULTIPLE CANCERS AND IS CONSIDERED AS A "CANCERIZATION FIELD", WITH OR WITHOUT EXPANSION OF PHYSIOLOGICAL PATCHES OF CLONAL CELLS. IN THIS REVIEW, WE DESCRIBE THE FORMATION OF A CANCERIZATION FIELD AND HOW WE CAN APPLY ITS DETECTION IN PRECISION CANCER RISK DIAGNOSIS. 2019 16 2852 38 FROM GASTRIC INFLAMMATION TO GASTRIC CANCER. THE MAJORITY OF GASTRIC ADENOCARCINOMAS ARE RELATED TO CHRONIC INFLAMMATION INDUCED BY HELICOBACTER PYLORI INFECTION. FOR INTESTINAL-TYPE GASTRIC CANCER, A MULTISTEP PROCESS OF MUCOSAL ALTERATIONS LEADING FROM GASTRITIS VIA GLANDULAR ATROPHY, INTESTINAL METAPLASIA AND DYSPLASIA TO INVASIVE CARCINOMA IS WELL RECOGNIZED. ONGOING CLINICAL STUDIES FOCUS ON A 'POINT OF NO RETURN'. IT IS DEFINED AS A SITUATION WHEN CERTAIN ALTERATIONS ARE NO LONGER REVERSIBLE BY H. PYLORI ERADICATION AND PROGRESSION TO GASTRIC CANCER MAY CONTINUE. H. PYLORI AFFECTS THE MUCOSAL AS WELL AS THE SYSTEMIC IMMUNE RESPONSE BY SECRETION OF CYTOKINES AND THE RECRUITMENT OF DISTINCT INFLAMMATORY CELLS. THE IMMUNE RESPONSE IS CHARACTERIZED BY A BALANCE BETWEEN A TH1-DOMINATED RESPONSE AND THE RECRUITMENT OF ANTIGEN-SPECIFIC REGULATORY T CELLS THAT ALLOW THE BACTERIA TO PERSIST IN HUMAN GASTRIC MUCOSA. BESIDES IMMUNE-MEDIATED EFFECTS, H. PYLORI INDUCES CELLULAR ALTERATIONS AS WELL AS GENETIC ALTERATIONS IN GENES THAT ARE ESSENTIAL FOR THE EPIGENETIC INTEGRITY AND MUCOSAL HOMEOSTASIS. THESE GENETIC ALTERATIONS DURING GASTRIC CANCER DEVELOPMENT ARE IN FOCUS OF INTENSIVE RESEARCH AND SHOULD ULTIMATELY ALLOW THE IDENTIFICATION OF RISK FACTORS INVOLVED IN GASTRIC CARCINOGENESIS. THE DETECTION OF INDIVIDUALS AT HIGH RISK FOR GASTRIC CANCER WOULD HELP TO DESIGN APPROPRIATE STRATEGIES FOR PREVENTION AND SURVEILLANCE. 2010 17 3683 37 INFLAMMATION, MICROBIOTA, AND PROSTATE CANCER. CONTEXT: CHRONIC INFLAMMATION OF THE PROSTATE HAS BEEN ASSOCIATED WITH PRENEOPLASTIC LESIONS AND CANCER DEVELOPMENT. MULTIPLE CAUSES HAVE BEEN CONSIDERED FOR CHRONIC INFLAMMATION OF THE PROSTATE. INFLAMMATORY CYTOKINES SUCH AS INTERLEUKINS ARE IMPLICATED IN PROSTATE CARCINOGENESIS AND DEVELOPMENT. OBJECTIVE: TO EVALUATE LITERATURE PUBLISHED ON ETIOLOGICAL FACTORS, URINARY MICROBIOTA, MORPHOLOGICAL FEATURES OF PROLIFERATIVE INFLAMMATORY ATROPHY AND HIGH-GRADE PROSTATE INTRAEPITHELIAL NEOPLASIA, GENETIC POLYMORPHISMS, INFLAMMATORY STRESS, AND CYTOKINE SIGNALING. EVIDENCE ACQUISITION: WE SEARCHED LITERATURE FROM PUBMED FROM 2010 AND ALSO INCLUDED THE MOST IMPORTANT PUBLICATIONS FROM THE PREVIOUS PERIOD. EVIDENCE SYNTHESIS: PROSTATE CANCER INFLAMMATION AND PREMALIGNANT LESIONS HAVE BEEN FREQUENTLY DISCUSSED IN SCIENTIFIC LITERATURE. A LIMITED NUMBER OF MODELS ARE AVAILABLE FOR STUDYING INFLAMMATION AND PREMALIGNANT LESIONS. HOWEVER, MORPHOLOGICAL PATHOLOGY COULD BE COMPLEMENTED BY ANALYSIS OF GENE POLYMORPHISMS IN THESE PATIENTS AND APPROPRIATE FUNCTIONAL STUDIES. CONCLUSIONS: PROSTATITIS COULD BE CAUSED BY BACTERIAL OR VIRAL INFECTIONS, DIETARY COMPOUNDS, AND CHANGES IN TESTOSTERONE:ESTRADIOL RATIO. IN SOME CASES, THE MICROBIOTA CAN EXERT DIRECT EFFECTS ON CANCER DEVELOPMENT. PROSTATE INFLAMMATORY ATROPHY OR HIGH GRADE PROSTATE INTRAEPITHELIAL NEOPLASIA HAVE BEEN ASSOCIATED WITH RESPONSE TO CELLULAR STRESS AND HAVE BEEN DISCUSSED IN CONNECTION TO EARLY CANCER DEVELOPMENT. A LARGE NUMBER OF GENETIC POLYMORPHISMS HAVE BEEN IDENTIFIED IN INFLAMMATORY PROSTATE. GENETIC AND EPIGENETIC ALTERATIONS MAY BE A CONSEQUENCE OF THE PROINFLAMMATORY STRESS IN THE PROSTATE. PROINFLAMMATORY CYTOKINES INTERLEUKIN-6 AND -8 CONTRIBUTE TO PROSTATE MALIGNANCY; HOWEVER, THEIR FUNCTION WAS MORE FREQUENTLY INVESTIGATED IN CANCER TISSUE RATHER THAN IN INFLAMMATION. PATIENT SUMMARY: WE PERFORMED A REVIEW OF RECENT LITERATURE RELATED TO PROSTATE INFLAMMATION, MICROBIOTA, AND PROSTATE CANCER. NEW FUNCTIONAL APPROACHES ARE REQUIRED FOR A BETTER UNDERSTANDING OF THE ROLE OF INFLAMMATION AND CANCER DEVELOPMENT. 2016 18 3038 31 GENOME ENGINEERING FOR OSTEOARTHRITIS: FROM DESIGNER CELLS TO DISEASE-MODIFYING DRUGS. BACKGROUND: OSTEOARTHRITIS (OA) IS A HIGHLY PREVALENT DEGENERATIVE JOINT DISEASE INVOLVING JOINT CARTILAGE AND ITS SURROUNDING TISSUES. OA IS THE LEADING CAUSE OF PAIN AND DISABILITY WORLDWIDE. AT PRESENT, THERE ARE NO DISEASE-MODIFYING OA DRUGS, AND THE PRIMARY THERAPIES INCLUDE EXERCISE AND NONSTEROIDAL ANTI-INFLAMMATORY DRUGS UNTIL TOTAL JOINT REPLACEMENT AT THE END-STAGE OF THE DISEASE. METHODS: IN THIS REVIEW, WE SUMMARIZED THE CURRENT STATE OF KNOWLEDGE IN GENETIC AND EPIGENETIC ASSOCIATIONS AND RISK FACTORS FOR OA AND THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. RESULTS: GENOME-WIDE ASSOCIATION STUDIES AND ANALYSIS OF EPIGENETIC MODIFICATIONS (SUCH AS MIRNA EXPRESSION, DNA METHYLATION AND HISTONE MODIFICATIONS) CONDUCTED ACROSS VARIOUS POPULATIONS SUPPORT THE NOTION THAT THERE IS A GENETIC BASIS FOR CERTAIN SUBSETS OF OA PATHOGENESIS. CONCLUSION: WITH RECENT ADVANCES IN THE DEVELOPMENT OF GENOME EDITING TECHNOLOGIES SUCH AS THE CRISPR-CAS9 SYSTEM, THESE GENETIC AND EPIGENETIC ALTERNATIONS IN OA CAN BE USED AS PLATFORMS FROM WHICH POTENTIAL BIOMARKERS FOR THE DIAGNOSIS, PROGNOSIS, DRUG RESPONSE, AND DEVELOPMENT OF POTENTIAL PERSONALIZED THERAPEUTIC TARGETS FOR OA CAN BE APPROACHED. FURTHERMORE, GENOME EDITING HAS ALLOWED THE DEVELOPMENT OF "DESIGNER" CELLS, WHEREBY THE RECEPTORS, GENE REGULATORY NETWORKS, OR TRANSGENES CAN BE MODIFIED AS A BASIS FOR NEW CELL-BASED THERAPIES. 2019 19 4994 32 PERFORMANCE OF DNA METHYLATION ON THE MOLECULAR PATHOGENESIS OF HELICOBACTER PYLORI IN GASTRIC CANCER; TARGETED THERAPY APPROACH. GASTRIC CANCER (GC) IS A SIGNIFICANT CAUSE OF CANCER MORTALITY WHICH HAS LED TO FOCUSED EXPLORATION OF THE PATHOLOGY OF GC. THE ADVENT OF GENOME-WIDE ANALYSIS METHODS HAS MADE IT POSSIBLE TO UNCOVER GENETIC AND EPIGENETIC FLUCTUATION SUCH AS ABNORMAL DNA METHYLATION IN GENE PROMOTER REGIONS THAT IS EXPECTED TO PLAY A KEY ROLE IN GC. THE STUDY OF GASTRIC MALIGNANCIES REQUIRES AN ETIOLOGICAL PERSPECTIVE, AND HELICOBACTER PYLORI (H. PYLORI) WAS IDENTIFIED TO PLAY A ROLE IN GC. H. PYLORI INFECTION CAUSES CHRONIC INFLAMMATION OF THE GASTRIC EPITHELIUM CAUSING ABNORMAL POLYCLONAL METHYLATION, WHICH MIGHT RAISE THE RISK OF GC. IN THE LAST TWO DECADES, VARIOUS PATHOGENIC FACTORS BY WHICH H. PYLORI INFECTION CAUSES GC HAVE BEEN DISCOVERED. ABNORMAL DNA METHYLATION IS TRIGGERED IN SEVERAL GENES, RENDERING THEM INACTIVE. IN GC, METHYLATION PATTERNS ARE LINKED TO CERTAIN SUBTYPES INCLUDING MICROSATELLITE INSTABILITY. MULTIPLE CANCER-RELATED PROCESSES ARE MORE USUALLY CHANGED BY ABNORMAL DNA METHYLATION THAN THROUGH MUTATIONS, ACCORDING TO CURRENT GENERAL AND COMBINED INVESTIGATIONS. FURTHERMORE, THE AMOUNT OF ACQUIRED ABNORMAL DNA METHYLATION IS HEAVILY LINKED TO THE CHANCES OF DEVELOPING GC. THEREFORE, WE INVESTIGATED ABNORMAL DNA METHYLATION IN GC AND THE LINK BETWEEN METHYLATION AND H. PYLORI INFECTION. 2022 20 5622 30 SEARCH FOR USEFUL BIOMARKERS IN HEPATOCELLULAR CARCINOMA, TUMOR FACTORS AND BACKGROUND LIVER FACTORS (REVIEW). HEPATOCARCINOGENESIS IS A COMPLEX AND MULTISTEP PROCESS THAT INVOLVES THE ACCUMULATION OF GENETIC AND EPIGENETIC ALTERATIONS IN REGULATORY GENES. TO UNDERSTAND THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA (HCC), CURRENT RESEARCH HAS UTILIZED IMPROVED ARRAY TECHNOLOGIES. THE IDENTIFICATION OF CANCER-RELATED MOLECULES COULD LEAD TO THE DEVELOPMENT OF NOVEL MOLECULAR TARGETS FOR TREATMENT AND BIOMARKERS FOR PREDICTING PROGNOSIS. HOWEVER, PROGNOSTIC PREDICTION IS INSUFFICIENT WHEN CONSIDERING ONLY TUMOR FACTORS, SINCE HEPATOCARCINOGENESIS IS ALSO GREATLY INFLUENCED BY THE STATUS OF THE BACKGROUND LIVER. CLINICAL BACKGROUND LIVER FACTORS, SUCH AS THE PRESENCE OF CHRONIC ACTIVE HEPATITIS OR CIRRHOSIS, ARE WELL KNOWN AS RISK FACTORS FOR DEVELOPING HCC. IN CONTRAST, GENETIC OR EPIGENETIC BACKGROUND LIVER FACTORS REMAIN UNKNOWN, ALBEIT THOSE ARE IMPORTANT TO UNDERSTAND THE DEVELOPING PROCESS OF HCC. INVESTIGATING BACKGROUND LIVER FACTORS COULD CONTRIBUTE TO THE DEVELOPMENT OF CARCINOGENIC MARKERS OF HCC AND TO THE PREVENTION OF THE DEVELOPMENT OF HCC. IN THE PRESENT STUDY, WE REVIEW THE CURRENTLY IDENTIFIED TUMOR FACTORS AND BACKGROUND LIVER FACTORS FROM A MOLECULAR BIOLOGICAL VIEWPOINT AND ALSO INTRODUCE OUR COMBINATION ARRAY ANALYSIS. 2017