Open AccessIdentification and validation of a novel signature for prediction the prognosis and immunotherapy benefit in bladder cancer
Author(s) -
Yichi Zhang,
Yaowang Lin,
Daojun Lv,
Xiangkun Wu,
Wenjie Li,
Xueqing Wang,
Dongmei Jiang
Publication year - 2022
Publication title -
peerj
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.927
H-Index - 70
ISSN - 2167-8359
DOI - 10.7717/peerj.12843
Subject(s) - immunotherapy , bladder cancer , proportional hazards model , gene signature , oncology , cancer immunotherapy , medicine , lasso (programming language) , population , gene expression , survival analysis , computational biology , cancer , gene , bioinformatics , biology , computer science , genetics , environmental health , world wide web
Background Bladder cancer (BC) is a common urinary tract system tumor with high recurrence rate and different populations show distinct response to immunotherapy. Novel biomarkers that can accurately predict prognosis and therapeutic responses are urgently needed. Here, we aim to identify a novel prognostic and therapeutic responses immune-related gene signature of BC through a comprehensive bioinformatics analysis. Methods The robust rank aggregation was conducted to integrate differently expressed genes (DEGs) in datasets of the Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO). Lasso and Cox regression analyses were performed to formulate a novel mRNA signature that could predict prognosis of BC patients. Subsequently, the prognostic value and predictive value of the signature was validated with two independent cohorts GSE13507 and IMvigor210. Finally, quantitative Real-time PCR (qRT-PCR) analysis was conducted to determine the expression of mRNAs in BC cell lines (UM-UC-3, EJ-1, SW780 and T24). Results We built a signature comprised the eight mRNAs: CNKSR1, COPZ2, CXorf57, FASN, PCOLCE2, RGS1, SPINT1 and TPST1. Our prognostic signature could be used to stratify BC population into two risk groups with distinct immune profile and responsiveness to immunotherapy. The results of qRT-PCR demonstrated that the eight mRNAs exhibited different expression levels in BC cell lines. Conclusion Our study constructed a convenient and reliable 8-mRNA gene signature, which might provide prognostic prediction and aid treatment decision making of BC patients in clinical practice.