Summary
Loss of the RASSF2A expression induced by methylation-mediated silencing has been reported in several human cancers, but the methylation status of RASSF2A in hepatocellular carcinoma (HCC) is rarely studied so far. In this study, we investigated the RASSF2A expression and its methylation status in a cohort of 45 hepatitis B virus-associated HCC tissues and their adjacent non-carcinoma tissues by using RT-PCR and MS-PCR. Promoter methylation of RASSF2A was found in 31 (68.9%) out of 45 HCC tissues and 12 (40%) out of 30 adjacent normal tissues, respectively (P<0.05). The methylation status of PASSF2A was closely associated with the loss of RASSF2A expression and elevated serum α-fetoprotein level, but not significantly with clinical stage, hepatic fibrosis and K-ras mutation. It was concluded that aberrant methylation of the RASSF2A gene with the subsequent loss of RASSF2A expression plays an important role in the pathogenesis of HCC.
Similar content being viewed by others
References
El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroen-terology, 2007, 132(7):2557–2576
Yao J, Yu W, Chang Y, et al. Targeted screening of siRNA directed HBV polymerase gene for effective inhibition of HBV expression. Huazhong Univ Sci Technolog Med Sci, 2008, 28(3):266–271
Hsu LS, Lee HC, Chau GY, et al. Aberrant methylation of EDNRB and p16 genes in hepatocellular carcinoma (HCC) in Taiwan. Oncol Rep, 2006, 15(2):507–511
Vos MD, Ellis CA, Elam C, et al. RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor. J Biol Chem, 2003, 278(30):28045–28051
Endoh M, Tamura G, Honda T, et al. RASSF2, a potential tumor suppressor, is silenced by CpG island hypermethylation in gastric cancer. Br J Cancer, 2005, 93(12): 1395–1399
Cooper WN, Dickinson RE, Dallol A, et al. Epigenetic regulation of the ras effector/tumor suppressor RASSF2 in breast and lung cancer. Oncogene, 2008, 27(12):1805–1811
Zhang Z, Sun D, Van do N, et al. Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma. Int J Cancer, 2007, 120(1):32–38
Imai T, Toyota M, Suzuki H, et al. Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma. Cancer Sci, 2008,99(5):958–966
Lee TL, Leung WK, Chan MW, et al. Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma. Clin Cancer Res, 2002, 8(6):1761–1766
Hatzaki A, Razi E, Anagnostopoulou K, et al. A modified mutagenic PCR-RFLP method for K-ras codon 12 and 13 mutations detection in NSCLC patients. Mol Cell Probes, 2001, 15(5):243–247
Ren JH, Lin JS, He WS, et al. RASSF2 induces activated Ras-dependent cell growth inhibition and apoptosis in human pancreatic cancer cells. J Cancer Mol, 2006, 2(3):117–122
Hesson LB, Wilson R, Morton D, et al. CpG island promoter hypermethylation of a novel Ras-effector gene RASSF2A is an early event in colon carcinogenesis and correlates inversely with K-ras mutations. Oncogene, 2005, 24(24):3987–3994
Park HW, Kang HC, Kim IJ, et al. Correlation between hypermethylation of the RASSF2A promoter and K-ras/BRAF mutations in microsatellite-stable colorectal cancers. Int J Cancer, 2007, 120(1):7–12
Harada K, Hiraoka S, Kato J, et al. Genetic and epigenetic alterations of Ras signalling pathway in colorectal neoplasia: analysis based on tumour clinicopathological features. Br J Cancer, 2007, 97(10):1425–1431
Peng SY, Chen WJ, Lai PL, et al. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer, 2004, 112(1):44–50
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ren, J., He, W., Zhang, R. et al. RASSF2A promoter methylation in hepatitis B virus-related hepatocellular carcinogenesis and its correlation with elevated serum α-fetoprotein level. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 29, 309–312 (2009). https://doi.org/10.1007/s11596-009-0309-8
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-009-0309-8