Hideki Yokoo, Tadashi Kondo, Testuya Okano, Tesshi Yamada, Satoru Todo, and Setsuo Hirohashi

Abstract

Poor prognosis of hepatocellular carcinoma (HCC) is mainly attributable to a high incidence of intrahepatic recurrence after surgery. To develop the accurate predictive marker for early intrahepatic recurrence and to identify therapeutic targets for the treatment of HCC patients, we examined protein expression profiles in HCC tissues using two-dimensional difference gel electrophoresis (2D-DIGE) representing approximately 1500 protein spots. An initial sample set (a training set) was comprised of 27 HCC patients; 12 patients who had intrahepatic recurrence within 6 months after curative surgery and 15 patients who did not have recurrence within 2 years. Using a supervised classification method based on support vector machine algorithm, we generated for the first time a proteomic signature, comprising of 23 protein spots, which associated with the early recurrence. The predictive performance of the signature was validated by a test set comprising 13 newly enrolled HCC patients; 6 early recurrence and 7 non-recurrence cases. The signature correctly classified 27 HCC patients in the training set, and predicted early recurrence in 12 (92.3%) of 13 patients on the test set with a positive predict value for 100% and a negative predict value of 85.7%. Mass spectrometric protein identification revealed that the proteins corresponding to the spots have the properties of oxidoreductases, chaperone, annexin and so on. In conclusion, we identified the proteomic signature, which can be a predictive marker for early intrahepatic recurrence. The proteins in the signature can also ne the therapeutic targets for HCC.

関連論文

1. Hideki Yokoo, Tadashi Kondo, Tetsuya Okano, Kazuaki Nakanishi, Michiie Sakamoto, Tomoo Kosuge, Satoru Todo and Setsuo Hirohashi. Protein expression associated with early intrahepatic recurrence of hepatocellular carcinoma after curative surgery. Cancer Sci, 98, 665-673, 2007. [PubMed]（外部リンク）