Prediction of sorafenib response by FGF3 gene amplification for patients with hepatocellular carcinoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 24240122
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Kinki University
• Principal Investigator: NISHIO Kazuto 近畿大学, 医学部, 教授 (10208134)
• Co-Investigator(Kenkyū-buntansha): KUDO Masatoshi 近畿大学, 医学部, 教授 (10298953)
• Project Period (FY): 2012-10-31 – 2015-03-31
• Keywords: 肝細胞がん / ソラフェニブ / バイオマーカー / TGF-α / PECAM1 / NRG1

Outline of Final Research Achievements

We have analyzed the copy number variation of hepatocellular carcinoma (HCC) tumor in a multicenter clinical study. We found increased copy number of FGF19 was a new predictive biomarker for sorafenib response in addition to FGF3/FGF4 gene amplification in HCC. Separately, we conducted DNA and RNA sequencing of tumor FFPE samples in another multicenter clinical trials for HCC patients treated with sorafenib. DNA amplicon sequencing and RNA sequencing targeted 50 candidate genes were performed using FFPE tumor samples obtained by liver core needle biopsy. HCC tumor with low oncogene mutation numbers were sensitive to sorafenib treatment, suggesting that oncogene mutational burden in the tumor might be associated with the clinical response to sorafenib. We have also identified candidate genes (TGF-, PECAM1, and NRG1) for the prediction of sorafenib response and progression free survival by RNA sequencing.

Free Research Field

分子生物学