PMID- 26660680 OWN - NLM STAT- MEDLINE DCOM- 20160801 LR - 20231213 IS - 1573-2568 (Electronic) IS - 0163-2116 (Linking) VI - 61 IP - 4 DP - 2016 Apr TI - Sera DNA Methylation of CDH1, DNMT3b and ESR1 Promoters as Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Hepatocellular Carcinoma. PG - 1130-8 LID - 10.1007/s10620-015-3975-3 [doi] AB - BACKGROUND: DNA methylation mainly affects tumor suppressor genes in the development of hepatocellular carcinoma (HCC). However, sera methylation of specific genes in hepatitis B virus (HBV)-related HCC remains unknown. AIMS: The purpose of this study was to identify methylation frequencies of sera E-cadherin (CDH1), DNA methyltransferase 3b (DNMT3b) and estrogen receptor 1 (ESR1) promoter in HBV-related HCC and analyze the associated clinical significance. METHODS: Methylation-specific PCR was used to determine the frequencies of DNA methylation for CDH1, DNMT3b and ESR1 genes in sera from 183 patients with HCC, 47 liver cirrhosis (LC), 126 chronic hepatitis B (CHB), and 50 normal controls (NCs). RESULTS: Significantly higher frequencies of methylation of CDH1, DNMT3b and ESR1 were found in HBV-related HCC compared with LC, CHB and NCs. Nodule numbers, tumor size and the presence of liver cirrhosis were significantly associated with gene methylation status in HBV-related HCC. Moreover, HBV may have a strong and enhanced effect on the concurrent methylation of CDH1, DNMT3b and ESR1 in HBV-related HCC. More importantly, combined methylation as a biomarker displayed significantly higher diagnostic value than AFP to discriminate HCC from CHB and LC. CONCLUSIONS: Aberrant sera DNA methylation of CDH1, DNMT3b and ESR1 gene promoters could be a biomarker in the early diagnosis of HBV-related HCC. FAU - Dou, Cheng-Yun AU - Dou CY AD - Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. FAU - Fan, Yu-Chen AU - Fan YC AD - Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. AD - Institute of Hepatology, Shandong University, Jinan, 250012, China. FAU - Cao, Chuang-Jie AU - Cao CJ AD - Department of Pathology, The First Affiliated Hospital of Sun Yat-san University, Guangzhou, 510080, China. FAU - Yang, Yang AU - Yang Y AD - Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. FAU - Wang, Kai AU - Wang K AD - Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. wangdoc876@126.com. AD - Institute of Hepatology, Shandong University, Jinan, 250012, China. wangdoc876@126.com. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151210 PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 0 (Antigens, CD) RN - 0 (Biomarkers) RN - 0 (CDH1 protein, human) RN - 0 (Cadherins) RN - 0 (ESR1 protein, human) RN - 0 (Estrogen Receptor alpha) RN - 0 (alpha-Fetoproteins) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) SB - IM MH - Adult MH - Aged MH - Antigens, CD MH - Biomarkers/*blood MH - Cadherins/genetics MH - Carcinoma, Hepatocellular/*blood/diagnosis/virology MH - Case-Control Studies MH - DNA (Cytosine-5-)-Methyltransferases/genetics MH - *DNA Methylation MH - Early Diagnosis MH - Estrogen Receptor alpha/genetics MH - Female MH - Hepatitis B, Chronic/*blood/complications MH - Humans MH - Liver Neoplasms/*blood/diagnosis/virology MH - Male MH - Middle Aged MH - Promoter Regions, Genetic MH - Prospective Studies MH - alpha-Fetoproteins/metabolism MH - DNA Methyltransferase 3B OTO - NOTNLM OT - CDH1 OT - DNMT3b OT - ESR1 OT - HBV-related HCC OT - Methylation EDAT- 2015/12/15 06:00 MHDA- 2016/08/02 06:00 CRDT- 2015/12/15 06:00 PHST- 2015/03/29 00:00 [received] PHST- 2015/11/13 00:00 [accepted] PHST- 2015/12/15 06:00 [entrez] PHST- 2015/12/15 06:00 [pubmed] PHST- 2016/08/02 06:00 [medline] AID - 10.1007/s10620-015-3975-3 [pii] AID - 10.1007/s10620-015-3975-3 [doi] PST - ppublish SO - Dig Dis Sci. 2016 Apr;61(4):1130-8. doi: 10.1007/s10620-015-3975-3. Epub 2015 Dec 10.