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Immune Related Signature Predicts the Prognosis and Immunotherapy Benefit in Bladder Cancer Through Immune Escape Mechanism

75 Pages Posted: 17 Nov 2019

See all articles by Yejinpeng Wang

Yejinpeng Wang

Wuhan University - Department of Urology

Liang Chen

Wuhan University - Department of Urology

Mengxue Yu

Wuhan University - Department of Biological Repositories

Yayun Fang

Wuhan University - Department of Biological Repositories

Kaiyu Qian

Wuhan University - Department of Biological Repositories

Gang Wang

Wuhan University - Department of Biological Repositories; Human Genetics Resource Preservation Center of Hubei Province; Wuhan University - Human Genetics Resource Preservation Center

Lingao Ju

Wuhan University - Department of Biological Repositories

Xinghuan Wang

Wuhan University - Department of Urology; Wuhan University - Center for Evidence-Based and Translational Medicine; Wuhan University - Medical Research Institute

Yu Xiao

Wuhan University - Department of Urology

More...

Abstract

Background: Immunotherapy has been applied to bladder cancer (BCa) for a long time. However, no signature is effective in predicting the benefit of immunotherapy for BCa.

Methods: Through The Least Absolute Shrinkage And Selection Operator (LASSO) algorithm, we constructed a 13-mRNA immune signature from the TCGA cohort, then the BCa immune microenvironment (TME) landscape was depicted based on the immune signature.

Findings: The immune signature could not only accurately predict the prognosis of BCa, but also the immunotherapy benefit. We validated its prognostic value with three independent external validation cohort. Our results indicating that high-risk group with higher inhibitory immune cell infiltration (regulatory T cells [Tregs] and macrophage, etc.), higher expression of immune checkpoints (programmed cell death protein-1 [PD-1], programmed death ligand-1 [PD-L1], cytotoxic T-lymphocyte associated protein 4 [CTLA4], etc.), and more T-cell suppressive pathways (transforming growth factor β [TGF-β], epithelial-mesenchymal transition [EMT], etc.) were activated, these together contribute to immune escape and might be the cause of poor prognosis. Besides, the immune signature showed a good predictive value for the benefit of immunotherapy in a cohort of urothelial carcinoma patients treated with PD-L1 (IMvigor210 cohort).

Interpretation: The immune signature constructed is convenient to classify the immunotherapeutic susceptibility of patients with BCa, so as to achieve precision immunotherapy for BCa.

Funding Statement: This work was supported by the Health commission of Hubei Province scientific research project (WJ2019H080, WJ2019H023 and WJ2019H013) and the Fundamental Research Funds for the Central Universities (2042019kf0150 and 2042019kf0176).

Declaration of Interests: The authors stated: "None."

Ethics Approval Statement: Not required.

Keywords: Bladder cancer (BCa); tumor microenvironment (TME); regulatory T cells (Tregs); macrophage; transforming growth factor β (TGF-β); programmed death ligand-1 (PD-L1)

Suggested Citation

Wang, Yejinpeng and Chen, Liang and Yu, Mengxue and Fang, Yayun and Qian, Kaiyu and Wang, Gang and Ju, Lingao and Wang, Xinghuan and Wang, Xinghuan and Xiao, Yu, Immune Related Signature Predicts the Prognosis and Immunotherapy Benefit in Bladder Cancer Through Immune Escape Mechanism (November 15, 2019). Available at SSRN: https://ssrn.com/abstract=3487678 or http://dx.doi.org/10.2139/ssrn.3487678

Yejinpeng Wang

Wuhan University - Department of Urology

China

Liang Chen

Wuhan University - Department of Urology

China

Mengxue Yu

Wuhan University - Department of Biological Repositories

Wuhan
China

Yayun Fang

Wuhan University - Department of Biological Repositories

Wuhan
China

Kaiyu Qian

Wuhan University - Department of Biological Repositories

Wuhan
China

Gang Wang

Wuhan University - Department of Biological Repositories ( email )

Wuhan
China

Human Genetics Resource Preservation Center of Hubei Province ( email )

Wuhan
China

Wuhan University - Human Genetics Resource Preservation Center ( email )

Wuhan
China

Lingao Ju

Wuhan University - Department of Biological Repositories

Wuhan
China

Xinghuan Wang (Contact Author)

Wuhan University - Department of Urology ( email )

China

Wuhan University - Center for Evidence-Based and Translational Medicine ( email )

China

Wuhan University - Medical Research Institute ( email )

Wuhan
China

Yu Xiao

Wuhan University - Department of Urology ( email )

China