New Prognostic Gene Signature and Immune Escape Mechanisms of Bladder Cancer

Yi Jiang; Zhenhao Zeng; Situ Xiong; Ming Jiang; Gaomin Huang; Chiyu Zhang; Xiaoqing Xi

doi:10.3389/fcell.2022.775417

New Prognostic Gene Signature and Immune Escape Mechanisms of Bladder Cancer

Front Cell Dev Biol. 2022 May 12:10:775417. doi: 10.3389/fcell.2022.775417. eCollection 2022.

Authors

Yi Jiang¹, Zhenhao Zeng², Situ Xiong², Ming Jiang², Gaomin Huang¹, Chiyu Zhang¹, Xiaoqing Xi¹

Affiliations

¹ Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
² Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Abstract

Background: The immune microenvironment profoundly affects tumor prognosis and therapy. The present study aimed to reveal potential immune escape mechanisms and construct a novel prognostic signature via systematic bioinformatic analysis of the bladder cancer (BLCA) immune microenvironment. Patients and Methods: The transcriptomic data and clinicopathological information for patients with BLCA were obtained from The Cancer Genome Atlas (TCGA). Consensus clustering analysis based on the CIBERSORT and ESTIMATE algorithms was performed with patients with BLCA, which divided them into two clusters. Subsequently, the differentially expressed genes (DEGs) in the two were subjected to univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to identify prognostic genes, which were used to construct a prognostic model. The predictive performance of the model was verified by receiver operating characteristic (ROC) and Kaplan-Meier (K-M) analyses. In addition, we analyzed the differentially altered immune cells, mutation burden, neoantigen load, and subclonal genome fraction between the two clusters to reveal the immune escape mechanism. Results: Based on the ESTIMATE and clustering analyses, patients with BLCA were classified into two heterogeneous clusters: ImmuneScoreH and ImmuneScoreL. Univariate Cox and LASSO regression analyses identified CD96 (HR = 0.83) and IBSP (HR = 1.09), which were used to construct a prognostic gene signature with significant predictive accuracy. Regarding potential immune escape mechanisms, ImmuneScoreH and ImmuneScoreL were characterized by inactivation of innate immune cell chemotaxis. In ImmuneScoreL, a low tumor antigen load might contribute to immune escape. ImmuneScoreH featured high expression of immune checkpoint molecules. Conclusion: CD96 and IBSP were considered prognostic factors for BLCA. Innate immune inactivation and a low tumor antigen load may be associated with immune escape mechanisms in both clusters. Our research complements the exploration of the immune microenvironment in BLCA.

Keywords: bladder cancer; gene signature; immune escape mechanism; immune microenvironment; prognosis.