Fibroblast Growth Factor Receptor 2 Is Associated With Poor Overall Survival in Clear Cell Carcinoma of the Ovary and May Be a Novel Therapeutic Approach
Fibroblast Growth Factor Receptor 2 Is Associated With Poor Overall Survival in Clear Cell Carcinoma of the Ovary and May Be a Novel Therapeutic Approach
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成纤维细胞生长因子受体 2 与卵巢透明细胞癌的总体生存率较差有关，可能是一种新的治疗方法
DOI：
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
T. Harada
中科院分区：
文献类型：
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作者：
H. Itamochi;Nao Oumi;T. Oishi;F. Taniguchi;T. Shoji;H. Fujiwara;T. Sugiyama;Mitsuaki Suzuki;J. Kigawa;T. Harada
目的我们发现卵巢透明细胞癌（CCC）中成纤维细胞生长因子受体（FGFR） 2基因和蛋白表达升高；在这里，我们检测了FGFR2在CCC肿瘤组织中的表达及其与临床参数的相关性。我们还分析了FGFR抑制剂对CCC细胞生长的影响，以研究FGFR2是否可以作为这种疾病的治疗靶点。方法通过免疫组织化学染色分析112例CCC患者中FGFR2的蛋白表达，并评估这些分子参数与临床预后的关系。我们用FGFR抑制剂处理了11个CCC细胞系，然后评估了细胞活力、FGFR2信号通路中蛋白质的表达和细胞周期分布。结果FGFR2在96%的CCC中表达。FGFR2中度或强表达患者的5年生存率显著低于FGFR2缺失或低表达患者（54% vs 79%）。多变量分析显示，FGFR2表达和疾病分期是独立的预后因素。FGFR抑制剂通过诱导G1细胞周期阻滞有效抑制CCC细胞的生长，下调磷酸化Akt和磷酸化ERK的表达。FGFR2是预测患者预后的重要生物标志物，是CCC的潜在靶点。FGFR抑制剂治疗CCC的进一步研究是必要的。
Objective We previously found that gene and protein expression of fibroblast growth factor receptor (FGFR) 2 were increased in ovarian clear cell carcinoma (CCC); here, we examined FGFR2 expression in CCC tumor tissues and its correlation with clinical parameters. We also analyzed the effect of an FGFR inhibitor on the growth of CCC cells to investigate whether FGFR2 could be a therapeutic target for this disease. Methods We analyze the protein expression of FGFR2 by immunohistochemical staining in CCC from 112 patients and evaluated the association of these molecular parameters with clinical outcome. We treated the 11 CCC cell lines with an FGFR inhibitor, and then assessed cell viability, the expression of protein in FGFR2 signaling pathway, and cell cycle distribution. Results The expressions of FGFR2 were found in 96% of CCC. The 5-year survival rate for patients with a moderate or strong expression of FGFR2 was significantly lower than that for those with an absent or poor expression of FGFR2 (54% vs 79%). Multivariable analysis revealed that FGFR2 expression and disease stage were independent prognostic factors. The FGFR inhibitor effectively suppressed the growth of CCC cells with induction of G1 cell cycle arrest and down-regulated the expression of phosphorylated Akt and phosphorylated ERK. Conclusions FGFR2 is an important biomarker predictive of patient outcome and is a potential target for CCC. Further study is warranted for FGFR inhibitor to treat CCC.
影响因子：
20.3
作者：
Trudel, S;Ely, S;Bergsagel, PL
通讯作者：
Bergsagel, PL
影响因子：
11.2
作者：
Byron, Sara A.;Gartside, Michael G.;Pollock, Pamela M.
通讯作者：
Pollock, Pamela M.