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

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

Research output: Contribution to journalArticle

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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 α-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.

Original languageEnglish
Pages (from-to)494-504
Number of pages11
JournalAnnals of Hepatology
Volume14
Issue number4
Publication statusPublished - 2015 Jan 1

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Fetal Proteins
DNA Methylation
Genetic Markers
Hepatocellular Carcinoma
Methylation
Serum
Genetic Promoter Regions
Genes
Disease-Free Survival
Proto-Oncogene Proteins p21(ras)
p16 Genes
Survival
Neoplasms
Cell Cycle
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Lin, Jin Ching ; Wu, Yao Chung ; Wu, Cheng Chung ; Shih, Pei Yin ; Wang, Wen Yi ; Chien, Yi-Chih. / DNA methylation markers and serum α-fetoprotein level are prognostic factors in hepatocellular carcinoma. In: Annals of Hepatology. 2015 ; Vol. 14, No. 4. pp. 494-504.
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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 α-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.",
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DNA methylation markers and serum α-fetoprotein level are prognostic factors in hepatocellular carcinoma. / Lin, Jin Ching; Wu, Yao Chung; Wu, Cheng Chung; Shih, Pei Yin; Wang, Wen Yi; Chien, Yi-Chih.

In: Annals of Hepatology, Vol. 14, No. 4, 01.01.2015, p. 494-504.

Research output: Contribution to journalArticle

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T1 - DNA methylation markers and serum α-fetoprotein level are prognostic factors in hepatocellular carcinoma

AU - Lin, Jin Ching

AU - Wu, Yao Chung

AU - Wu, Cheng Chung

AU - Shih, Pei Yin

AU - Wang, Wen Yi

AU - Chien, Yi-Chih

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Y1 - 2015/1/1

N2 - 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 α-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.

AB - 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 α-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.

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