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DNA methylation markers and serum alpha-fetoprotein level are prognostic factors in hepatocellular carcinoma

Jin-Ching Lin, Yao-Chung Wu, Cheng-Chung Wu, Pei-Yin Shih Shih, Wen-Yi Wang, Yi-Chih Chien

Abstract

Introduction. Hypermethylation of relevant genes may affect the prognosis of patients with cancer. The purpose of this study was to analyze whether methylation of the promoter regions of cell cycle regulators as well as elevated alpha-Fetoprotein (AFP) levels are useful prognostic factors for patients with hepatocellular carcinoma (HCC). Material and methods. Nested methylation-specific PCR (nested-MSP) was used to analyze methylation status of the promoter regions of p15, p16, p21, p27, and ras-association domain family 1 (RASSF1A) genes in tumor specimens from 50 patients with HCC. Results. Promoter methylation was most common in the RASSF1A gene (96%), followed by the p16 gene (56%), the p21 gene (44%), the p15 gene (28%), and the p27 gene (2%). Patients with a serum AFP level < 400 ng/mL and an unmethylated p21 promoter had a better prognosis than patients with a serum AFP level ? 400 ng/mL and a methylated p21 promoter (overall survival, p = 0.076; disease-free survival, p = 0.016). In addition, patients with full methylation of the promoter region of RASSF1A had a better prognosis than patients with a partially methylated or unmethylated RASSF1A promoter region if their serum AFP level was ? 400 ng/mL (overall survival, p = 0.028; disease-free survival, p = 0.078). Conclusion. A partially methylated or unmethylated RASSF1A promoter as well as elevated serum AFP level or methylation of p21 in addition to elevated serum AFP level might be associated with poor prognosis in patients with hepatocellular carcinoma.

Key words. Hepatocellular carcinoma (HCC)., Methylation., alpha-fetoprotein (AFP)., Ras-association domain family 1(RASSF1A)., p21.

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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