Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma

Eri Arai, Saori Ushijima, Masahiro Gotoh, Hidenori Ojima, Tomoo Kosuge, Fumie Hosoda, Tatsuhiro Shibata, Tadashi Kondo, Sana Yokoi, Issei Imoto, Johji Inazawa, Setsuo Hirohashi, Yae Kanai

研究成果: Article査読

49 被引用数 (Scopus)

抄録

To clarify genome-wide DNA methylation profiles during hepatocarcinogenesis, bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed on 126 tissue samples. The average numbers of BAC clones showing DNA hypo- or hypermethylation increased from noncancerous liver tissue obtained from patients with hepatocellular carcinomas (HCCs) (N) to HCCs. N appeared to be at the precancerous stage, showing DNA methylation alterations that were correlated with the future development of HCC. Using Wilcoxon test, 25 BAC clones, whose DNA methylation status was inherited by HCCs from N and were able to discriminate 15 N samples from 10 samples of normal liver tissue obtained from patients without HCCs (C) with 100% sensitivity and specificity, were identified. The criteria using the 25 BAC clones were able to discriminate 24 additional N samples from 26 C samples in the validation set with 95.8% sensitivity and 96.2% specificity. Using Wilcoxon test, 41 BAC clones, whose DNA methylation status was able to discriminate patients who survived more than 4 years after hepatectomy from patients who suffered recurrence within 6 months and died within a year after hepatectomy, were identified. The DNA methylation status of the 41 BAC clones was correlated with the cancer-free and overall survival rates of patients with HCC. Multivariate analysis revealed that satisfying the criteria using the 41 BAC clones was an independent predictor of overall outcome. Genome-wide alterations of DNA methylation may participate in hepatocarcinogenesis from the precancerous stage, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication.

本文言語English
ページ(範囲)2854-2862
ページ数9
ジャーナルInternational Journal of Cancer
125
12
DOI
出版ステータスPublished - 2009 12 15
外部発表はい

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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