Somatic FGFR3 Mutations Distinguish a Subgroup of Muscle-Invasive Bladder Cancers with Response to Neoadjuvant ChemotherapyResearch in Context
Zhao Yang,
Ruiyun Zhang,
Yunxia Ge,
Xuying Qin,
Xing Kang,
Yue Wang,
Xu Zhang,
Chengli Song,
Xiaofang Quan,
Haifeng Wang,
Haige Chen,
Chong Li
Affiliations
Zhao Yang
Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Laboratory of Biomanufacturing and Food Engineering, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China
Ruiyun Zhang
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Yunxia Ge
Novogene Bioinformatics Technology Co., Ltd, Beijing 100083, China
Xuying Qin
Beijing Taipu-Shunkang Institute For Laboratory Medicine, Beijing 100076, China
Xing Kang
Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Yue Wang
Novogene Bioinformatics Technology Co., Ltd, Beijing 100083, China
Xu Zhang
Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Chengli Song
Novogene Bioinformatics Technology Co., Ltd, Beijing 100083, China
Xiaofang Quan
Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Haifeng Wang
Department of Urology, The Second Affliated Hospital of Kunming Medical University, Kunming 650101, China
Haige Chen
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; Corresponding author at: Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201112, China.
Chong Li
Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Department of Urology, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen 518000, China; Beijing Jianlan Institute of Medicine, Beijing 100190, China; Corresponding author at: Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
The administration of neoadjuvant chemotherapy (NAC) preceding radical cystectomy benefits overall survival for patients with muscle-invasive bladder cancer (MIBC). However, the relationship between the genetic profiling of MIBC and NAC response remains unclear. Here, a mutation panel of six cancer-associated genes (TSC1, FGFR3, TERT, TP53, PIK3CA and ERBB2) and an immunohistochemistry (IHC) panel containing eight bladder cancer (BC) biomarkers (EGFR, RRM1, PD-L1, BRCA1, TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin α3β1 (AG) and CK5/6) were developed. BC samples from patients who showed a pathologic response (n = 39) and non-response (n = 13) were applied to the panel analysis. ERBB2, FGFR3 and PIK3CA exclusively altered in the responders group (19/39, 48.7%), in which FGFR3 mutations were significantly enriched in patients with a response in the cohort (14/39, 35.9%; P = 0.01). Additionally, strong expression of ERCC1 was associated with a pathologic response (P = 0.01). However, positive lymph node metastasis (P < 0.01) and lymph-vascular invasion (LVI) (P = 0.03) were correlated with a non-response. Overall, the data show that FGFR3 mutations and elevated expression of ERCC1 in MIBCs are potential predictive biomarkers of the response to NAC. Keywords: Bladder cancer, Neoadjuvant chemotherapy, FGFR3, ERCC1
