Abstract
Abstract Genomic variation of FGFR has been intensively investigated in cancer for years, however, clinical trials on the basis of FGFR mutation or amplification as a druggable target of FGFR inhibitors have produced disappointing clinical outcomes. Therefore, the identification of predictive biomarkers for FGFR-targeted agents has remained a crucial issue. Expression profiles of FGF and FGFR in 8,111 patients with 24 types of solid tumors and 879 tumor cell lines along with drug sensitivity data were obtained from public databases. Differential expression, survival and correlation analyses were performed to uncover the clinical relevance of FGF and FGFR genes expression in pan-cancer. As results, FGF and FGFR were frequently dysregulated in pan-cancer. Moreover, almost all the FGF and FGFR were significantly associated with overall survival in at least two cancer types, however, mixed prognostic values were seen in pan-cancer. More importantly, tumor cell lines with high FGFR1/3 expression were more sensitive to FGFR inhibitor PD173074, especially in breast cancer, liver cancer, lung squamous cell carcinoma and ovarian cancer. The predicted positive ratios of FGFR1/2/3/4 were generally over 10% in most tumor types, especially in squamous cell carcinoma. High positive FGFR1 or 3 expression ratio were predicted in cholangiocarcinoma (58%), followed by bladder cancer (42%), endometrial carcinoma (35%), ovarian cancer (34%) and head and neck squamous cell carcinoma (34%). FGFR expression were promising predictive biomarkers for FGFR inhibition response in clinical trials and different combination of FGFR genes should be used in screening for patients in certain tumor types. Citation Format: Yuan Li, Long Wu, Yanlei Cheng, Weiping Tao, Dawei Wu, Fei Ma, Ning Li. Expression atlas of FGF and FGFR genes in pan-cancer uncovered predictive biomarkers for FGFR inhibition response in clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4882.
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