Clinicopathological significance of RASSF1A reduced expression and hypermethylation in hepatocellular carcinoma
- 29 January 2010
- journal article
- Published by Springer Science and Business Media LLC in Hepatology International
- Vol. 4 (1), 423-432
- https://doi.org/10.1007/s12072-010-9164-8
Abstract
Protein downregulation and hypermethylation of Ras association domain family 1A (RASSF1A) has been recognized as an important early event in different classes of carcinogenesis, but clinicopathological significance of RASSF1A protein expression and methylation in hepatocellular carcinoma (HCC) remains largely unknown. The aim of the study was to investigate the expression of RASSF1A protein and methylation in HCC and their clinical significance. Immunohistochemistry was employed to detect the expression of RASSF1A proteins in liver tissue microarrays. Aberrant promoter hypermethylation of RASSF1A was investigated in DNA from HCC, matching noncancerous tissues and serum of 35 HCC patients by methylation-specific PCR. RASSF1A protein expression in HCC was significantly lower than that in noncancerous (p = 0.015) and paracancerous tissues (p = 0.017). In addition, reduced RASSF1A protein expression is related to TNM stage, metastasis, α-fetoprotein, portal vein embolus, capsular infiltration, and multiple tumor nodes. Furthermore, RASSF1A promoter methylation in HCC was significantly higher than that in noncancerous liver tissues (p < 0.05). Meanwhile, RASSF1A promoter hypermethylation was detected in 14 in the serum DNA from HCC patients, whereas no hypermethylation was detected in the normal controls. Hypermethylation of RASSF1A in HCC serum and tissues was negatively correlated with the expression of RASSF1A protein expression (p < 0.05). The loss or abnormal protein downregulation and the promoter hypermethylation of RASSF1A could play important roles in the tumorigenesis development and metastases of HCC. The detection of the promoter hypermethylation of RASSF1A in serum DNA could be a valuable biomarker for early-stage diagnosis in populations at high risk of HCC.Keywords
This publication has 36 references indexed in Scilit:
- RASSF1A expression inhibits the growth of hepatocellular carcinoma from Qidong CountyJournal of Gastroenterology and Hepatology, 2008
- Reduced expression of RASSF1A in esophageal and nasopharyngeal carcinomas significantly correlates with tumor stageCancer Letters, 2007
- Mahanine reverses an epigenetically silenced tumor suppressor gene RASSF1A in human prostate cancer cellsBiochemical and Biophysical Research Communications, 2007
- Differences of HBV genotypes and hepatocellular carcinoma in Asian countriesHepatology Research, 2007
- Association of diminished expression of RASSF1A with promoter methylation in primary gastric cancer from patients of central ChinaBMC Cancer, 2007
- Predicting Hepatocellular Carcinoma by Detection of Aberrant Promoter Methylation in Serum DNAClinical Cancer Research, 2007
- The Significance of c-erbB-2 Overexpression and p53 Expression in Patients With Axillary Lymph Node—Negative Breast Cancer: A Tissue Microarray StudyInternational Journal of Surgical Pathology, 2007
- CpG Island Methylator Phenotype Association with Elevated Serum α-Fetoprotein Level in Hepatocellular CarcinomaClinical Cancer Research, 2007
- Quantitative evaluation of RASSF1Amethylation in the non-lesional, regenerative and neoplastic liverBMC Cancer, 2006
- High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinomaLiver International, 2005