がんのプロテオーム解析による個別化医療のためのバイオマーカー開発

抄録

Cancer is a diverse disease, and the present clinical and pathological diagnostic modalities have obvious limitation in the prediction of clinical outcome. The next level of predictive molecular diagnostics is expected to best-optimize the existing therapeutic strategy. We examined proteome contents in more than 1,000 tumor tissues using our original large format two-dimensional difference gel electrophoresis (2D-DIGE) system. By integrating 2D-DIGE data with clinico-pathological parameters, we concluded that proteomics has a great potential to identify biomarker candidate proteins. For instance, 2D-DIGE experiments using clinical samples detected key proteins corresponding to the response to treatment in lung adenocarcinoma, osteosarcoma and Ewing sarcoma, the early recurrence in liver cancer, the lymph node metastasis of esophageal cancer, and the metastasis post surgery in gastrointestinal stromal tumor. The predictive performance of the identified protreins was successfully validated in more than 100 cases by immunohistochemistry. Such proteins should be strong candidates for biomarkers for personalized medicine. The clinical application of these research results is our next challenge. To facilitate the integrative and comprehensive omics study, we take a part of Genome Medicine Database of Japan. All proteome data by 2D-DIGE, protein annotations and clinico-pathologidal data are currently integrated into this database. We strongly believe that cancer proteomics is a powerful tool for biomarker development, and its practical utilities will be proven in the very near future.

References
1. T. Kondo and S. Hirohashi, Nat Protoc. 1, 2940-2956, 2006.
2. T. Okano and T. Kondo et al, Clin. Cancer Res. 13, 799-805, 2007.
3. Y. Suehara and T. Kondo et al, Clin. Cancer Res. 14, 1707-1717, 2008.
4. GeMDBJ Proteomics, https://gemdbj.nibio.go.jp/dgdb/DigeTop.do