Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment.
Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment.
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DOI：
10.18632/oncotarget.10077
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发表时间：
2016-08-02
期刊：
影响因子：
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通讯作者：
Nishio K
中科院分区：
文献类型：
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作者：
Kaibori M;Sakai K;Ishizaki M;Matsushima H;De Velasco MA;Matsui K;Iida H;Kitade H;Kwon AH;Nagano H;Wada H;Haji S;Tsukamoto T;Kanazawa A;Takeda Y;Takemura S;Kubo S;Nishio K
多激酶抑制剂索拉非尼在临床上被批准用于治疗晚期肝细胞癌（HCC）患者。我们以前报道，成纤维细胞生长因子3和4（FGF 3/FGF 4）扩增是索拉非尼反应的预测因子。本研究旨在分析FGF-FGF受体（FGFR）基因改变与索拉非尼疗效之间的关系。收集来自索拉非尼治疗后达到完全缓解（CR，N=6）或非CR（N=39）的HCC患者的福尔马林固定、石蜡包埋组织标本，并使用下一代测序和拷贝数测定法检查FGF-FGFR基因改变。在45例病例中的5例（11.1%）中检测到FGFR突变。FGFR突变状态与索拉非尼治疗反应之间无显著相关性。在CR病例中，我们没有检测到FGF 3/FGF 4拷贝数的增加。在CR病例（2/6，33.3%）中检测到FGF 19拷贝数增加的频率高于非CR病例（2/39，5.1%）（P = 0.024，卡方检验）。总之，除了FGF 3/FGF 4扩增之外，FGF 19的拷贝数增加可能是对索拉非尼的反应的预测因子。
The multi-kinase inhibitor sorafenib is clinically approved for the treatment of patients with advanced hepatocellular carcinoma (HCC). We previously reported that fibroblast growth factor 3 and 4 (FGF3/FGF4) amplification is a predictor of a response to sorafenib. This study aims to analyze the relationship between FGF-FGF receptor (FGFR) genetic alterations and the response to sorafenib. Formalin-fixed, paraffin-embedded tissue specimens from HCC patients who had achieved a complete response (CR, N=6) or non-CR (N=39) to sorafenib were collected and were examined for FGF-FGFR gene alterations using next generation sequencing and copy number assay. FGFR mutations were detected in 5 of 45 (11.1%) cases. There was no significant association between FGFR mutation status and the response to sorafenib. We detected no increase in the FGF3/FGF4 copy number in CR cases. An FGF19 copy number gain was detected more frequently among CR cases (2/6, 33.3%) than among non-CR cases (2/39, 5.1%) (P = 0.024, Chi-squared test). In conclusion, a copy number gain for FGF19 may be a predictor of a response to sorafenib, in addition to FGF3/FGF4 amplification.