Mitochondrial metabolism in the noncancerous liver determine the occurrence of hepatocellular carcinoma: A prospective study

Atsushi Kudo, Kaoru Mogushi, Tadatoshi Takayama, Satoshi Matsumura, Daisuke Ban, Takumi Irie, Takanori Ochiai, Noriaki Nakamura, Hiroshi Tanaka, Naohiko Anzai, Michiie Sakamoto, Shinji Tanaka, Shigeki Arii

研究成果: Article査読

14 被引用数 (Scopus)

抄録

Background: Recurrence determines the postoperative prognosis with hepatocellular carcinoma (HCC). It is unknown how the liver dysfunction involving organic anion transporter failure causes the occurrence of HCCs. This study was designed to elucidate the link between liver dysfunction and multicentric occurrence (MO) after radical hepatectomy. Methods: Forty-nine samples of noncancerous liver tissue from HCC patients within the Milan criteria who were treated at our institution between January 2004 and August 2008 were examined as a training set by using genome-wide gene expression analysis. Using the independent 2-institutional cohort of 134 patients between September 2008 and December 2009, we performed a validation study using tissue microarray analysis. Cox proportional hazard regression analyses for MFS were performed to estimate the risk factors. Results: In the Gene Ontology database (GO:0015711), SLC22A7 expression was the best predictor of MO-free survival [MFS] (Fold, 0.726; P = 0.001). High SLC22A7 gene expression prevented the occurrence of HCC after hepatectomy (odds ratio [OR], 0.2; P = 0.004). Multivariate analyses identified SLC22A7 expression as an independent risk factor (OR, 0.3; P = 0.043). In the validation study, multivariate analyses of MFS identified SLC22A7 expression as an independent risk factor (OR, 0.5; P = 0.012). As judged by gene set enrichment analysis, SLC22A7 down regulation was associated with mitochondrion (P = 0.008) and oxidoreductase activity (P = 0.006). Sirtuin 3 as a regulator of mitochondrial metabolism also determined MFS (P = 0.018). Conclusions: The mitochondrial pathways may affect SLC 22A7 function to promote the occurrence of HCC. (Word count: 246).

本文言語English
ページ(範囲)502-510
ページ数9
ジャーナルJournal of gastroenterology
49
3
DOI
出版ステータスPublished - 2014 3月

ASJC Scopus subject areas

  • 消化器病学

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