Cheng-Yun Dou1, Yu-Chen Fan1,2, Chuang-Jie Cao3, Yang Yang1, Kai Wang4,5. 1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. 2. Institute of Hepatology, Shandong University, Jinan, 250012, China. 3. Department of Pathology, The First Affiliated Hospital of Sun Yat-san University, Guangzhou, 510080, China. 4. Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China. wangdoc876@126.com. 5. Institute of Hepatology, Shandong University, Jinan, 250012, China. wangdoc876@126.com.
Abstract
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.
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.
Authors: Jorge A Marrero; Ziding Feng; Yinghui Wang; Mindie H Nguyen; Alex S Befeler; Lewis R Roberts; K Rajender Reddy; Denise Harnois; Josep M Llovet; Daniel Normolle; Jackie Dalhgren; David Chia; Anna S Lok; Paul D Wagner; Sudhir Srivastava; Myron Schwartz Journal: Gastroenterology Date: 2009-04-09 Impact factor: 22.682