Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi, 214000, People's Republic of China.
Department of Pathology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinglong Road, Changzhou, 213003, People's Republic of China.
Sci Rep. 2021 Jan 14;11(1):1373. doi: 10.1038/s41598-020-80146-y.
The correlation between G388R or V10I polymorphisms of fibroblast growth factor receptor (FGFR) 4 gene and the risk of carcinoma has been investigated previously, but the results are contradictory. Odds ratios (ORs) with 95% confidence intervals (95%CIs), in silico tools, and immunohistochemical staining (IHS) were adopted to assess the association. In total, 13,793 cancer patients and 16,179 controls were evaluated in our pooled analysis. Summarization of all the studies showed that G388R polymorphism is associated with elevated susceptibility to cancer under homozygous comparison (OR = 1.21, 95%CI = 1.03-1.43, P = 0.020) and a recessive genetic model (OR = 1.21, 95%CI = 1.04-1.41, P = 0.012). In the stratification analysis by cancer type and ethnicity, similar findings were indicated for prostate cancer, breast cancer, and individuals of Asian descendant. Polyphen2 bioinformatics analysis showed that the G388R mutation is predicted to damage the protein function of FGFR4. IHS analysis indicated that FGFR4 expression is increased in advanced prostate cancer. These findings may guide personalized treatment of certain types of cancers. Up-regulation of FGFR4 may be related to a poor prognosis in prostate cancer.
先前已经研究了成纤维细胞生长因子受体 (FGFR) 4 基因的 G388R 或 V10I 多态性与癌症风险之间的相关性，但结果存在矛盾。采用比值比 (OR) 和 95%置信区间 (95%CI)、计算机模拟工具和免疫组织化学染色 (IHS) 来评估相关性。在我们的汇总分析中，共评估了 13793 名癌症患者和 16179 名对照者。所有研究的综合结果表明，G388R 多态性与同合子比较下癌症易感性升高相关（OR=1.21，95%CI=1.03-1.43，P=0.020）和隐性遗传模型（OR=1.21，95%CI=1.04-1.41，P=0.012）。按癌症类型和种族进行分层分析，前列腺癌、乳腺癌和亚洲后裔个体也得到了类似的发现。Polyphen2 生物信息学分析表明，G388R 突变预计会破坏 FGFR4 的蛋白质功能。IHS 分析表明，FGFR4 在晚期前列腺癌中表达增加。这些发现可能为某些类型的癌症的个体化治疗提供指导。FGFR4 的上调可能与前列腺癌的预后不良有关。
