New Prognostic Gene Signature and Immune Escape Mechanisms of Bladder Cancer

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.

Pan-cancer analysis shows that IBSP is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including osteosarcoma

“…Therefore, some studies have revealed that IBSP promotes bone metastasis of tumor cells in BRCA ( 9 ), PRAD ( 27 ), and non-small cell lung cancer ( 21 ). Recently, with the development of bioinformatics, some studies demonstrated that the expression of IBSP is upregulated in epithelial tumors such as laryngeal cancer ( 28 ) and BLCA ( 29 ), which is highly correlated with a poor prognosis. For malignant tumors of non-epithelial origin, such as GBM, IBSP can also promote tumor cell proliferation and migration ( 30 ).…”

Construction of a prediction model for prognosis of bladder cancer based on the expression of ion channel-related genes

“…基于11个与膀胱癌预后相关的ICRG建立膀胱癌预后评分方程，回归分析显示该风险评分是膀胱癌患者预后的独立影响因素。结合临床特征构建的列线图也展示出对膀胱癌患者预后较好的预测价值。与其他基因集构建的膀胱癌预后风险评估模型比较，本研究构建的模型在预测膀胱癌患者5年存活率方面有着更高的效能 ［ 18 ， 52 ］ 。此外，相比Liang等 ［ 53 ］ 构建的15个基因的模型，本研究构建的模型纳入的基因数较少，检验难度小，便于应用于临床。本研究还发现风险评分与肿瘤免疫细胞浸润密切相关。浆细胞、活化NK细胞、静息肥大细胞免疫浸润水平在低风险组患者中显著上调，而在高风险组中M2型巨噬细胞浸润水平明显高于低风险组，提示高风险组患者存在免疫抑制微环境。上述研究结果可以为膀胱癌患者的免疫治疗提供一定的参考。…”

Identification and verification of anoikis-related gene markers to predict the prognosis of patients with bladder cancer and assist in the diagnosis and treatment of bladder cancer

“…However, the 5-year survival rate and median survival of bladder cancer are still difficult to achieve satisfactory results ( 6 - 8 ). With the development of bioinformatics technology, more and more literature shows that genes can be used as biomarkers for prognosis prediction of bladder cancer ( 9 - 13 ).…”