Oxidative stress pathways in noncancerous human liver tissue to predict hepatocellular carcinoma recurrence: A prospective, multicenter study

Shinji Tanaka, Kaoru Mogushi, Mahmut Yasen, Daisuke Ban, Norio Noguchi, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Hiroshi Tanaka, Masakazu Yamamoto, Norihiro Kokudo, Tadatoshi Takayama, Seiji Kawasaki, Michiie Sakamoto, Shigeki Arii

研究成果: Article査読

23 被引用数 (Scopus)

抄録

The prediction of cancer recurrence holds the key to improvement of the postoperative prognosis of patients. In this study, the recurrence of early-stage hepatocellular carcinoma (HCC) after curative hepatectomy was analyzed by the genome-wide gene-expression profiling on cancer tissue and the noncancerous liver tissue. Using the training set of 78 cases, the cytochrome P450 1A2 (CYP1A2) gene in noncancerous liver tissue was identified as the predictive candidate for postoperative recurrence (hazard ratio [HR], 0.447; 95% confidence interval [CI], 0.249-0.808; P = 0.010). Multivariate analysis revealed the statistically significant advantage of CYP1A2 down-regulation to predict recurrence (odds ratio, 0.534; 95% CI, 0.276-0.916; P = 0.036), and the expression of CYP1A2 protein was confirmed immunohistochemically. An independently multi-institutional cohort of 211 patients, using tissue microarrays, validated that loss of expression of CYP1A2 in noncancerous liver tissue as the only predictive factor of recurrence after curative hepatectomy for early-stage HCC (HR, 0.480; 95% CI, 0.256-0.902; P = 0.038). Gene set-enrichment analysis revealed close association of CYP1A2 down-regulation with oxidative stress pathways in liver tissue (P < 0.001, false discovery rate [FDR] = 0.042; P = 0.006, FDR = 0.035). Our results indicate these pathways as the molecular targets to prevent recurrence, as well as the potential prediction of the super high-risk population of HCC using liver tissue.

本文言語English
ページ(範囲)1273-1281
ページ数9
ジャーナルHepatology
54
4
DOI
出版ステータスPublished - 2011 10

ASJC Scopus subject areas

  • 肝臓学

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