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Specific Gene-Expression Profiles of Noncancerous Liver Tissue Predict the Risk for Multicentric Occurrence of Hepatocellular Carcinoma in Hepatitis C Virus–Positive Patients

¹ Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Tsurumihara 4546, Beppu, 874-0838, Japan
² Department of Surgery, Iizuka Hospital, Iizuka, Japan
³ Department of Digestive Surgery, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan
⁴ Department of Surgery, Oita Red Cross Hospital, Oita, Japan
⁵ Department of Surgery, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan
⁶ Laboratory for Bioinformatics, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan

Correspondence: Address correspondence and reprint requests to: Masaki Mori, MD; E-mail: mmori{at}beppu.kyushu-u.ac.jp.

Background: Hepatitis C virus (HCV) infection produces chronic hepatitis, cirrhosis, and, ultimately, hepatocellular carcinoma (HCC). A molecular analysis of the damaged liver tissues infected with HCV may identify specific gene-expression profiles associated with a risk for liver carcinogenesis.

Methods: Forty patients with HCV-positive HCC were classified into two groups: single nodular HCC group (n = 28) and multicentric HCC group (n = 12). Using a complementary DNA microarray, we compared the gene-expression patterns of the noncancerous liver tissue specimens between the two groups. We also identified the differentially expressed genes related to multicentric recurrence in the liver remnant. We then evaluated whether a specific gene-expression profile can accurately estimate the risk for multicentric hepatocarcinogenesis.

Results: We selected the 230 differentially expressed genes in the multicentric HCC group. A hierarchical clustering analysis identified a cluster that might be closely associated with the multicentric occurrence of HCC. On the basis of the gene-expression profiling of the 36 genes commonly associated with both multicentric HCC and multicentric recurrence, we created a scoring system to estimate the risk for multicentric hepatocarcinogenesis. The prediction score of patients in the multicentric HCC group with multicentric recurrence (19.9 ± 9.2) was significantly higher (P < .05) than that in the single nodular HCC group without multicentric recurrence (–1.8 ± 12.7).

Conclusions: Specific gene-expression signatures in noncancerous liver tissue may help to accurately predict the risk for developing HCC.

Key Words: Hepatocellular carcinoma • Multicentric occurrence • Hepatitis C virus • DNA microarray

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