Identification and Immunocorrelation of Prognosis-Related Genes Associated With Development of Muscle-Invasive Bladder Cancer

Abstract

Improved understanding of the molecular mechanisms and immunoregulation of muscle-invasive bladder cancer (MIBC) is essential to predict prognosis and develop new targets for therapies. In this study, we used the cancer genome atlas (TCGA) MIBC and GSE13507 datasets to explore the differential co-expression genes in MIBC comparing with adjacent non-carcinoma tissues. We firstly screened 106 signature genes by Weighted Gene Co-expression Network Analysis (WGCNA) and further identified 15 prognosis-related genes of MIBC using the univariate Cox progression analysis. Then we systematically analyzed the genetic alteration, molecular mechanism, and clinical relevance of these 15 genes. We found a different expression alteration of 15 genes in MIBC comparing with adjacent non-carcinoma tissues and normal tissues. Meanwhile, the biological functions and molecular mechanisms of them were also discrepant. Among these, we observed the ANLN was highly correlated with multiple cancer pathways, molecular function, and cell components, revealing ANLN may play a pivotal role in MIBC development. Next, we performed a consensus clustering of 15 prognosis-related genes; the results showed that the prognosis, immune infiltration status, stage, and grade of MIBC patients were significantly different in cluster1/2. We further identified eight-genes risk signatures using the least absolute shrinkage and selection operator (LASSO) regression analysis based on the expression values of 15 prognosis-related genes, and also found a significant difference in the prognosis, immune infiltration status, stage, grade, and age in high/low-risk cohort. Moreover, the expression of PD-1, PD-L1, and CTLA4 was significantly up-regulated in cluster1/high-risk-cohort than that in cluster2/low-risk-cohort. High normalized enrichment score of the Mitotic spindle, mTORC1, Complement, and Apical junction pathway suggested that they might be involved in the distinct tumor immune microenvironment (TIME) of cluster1/2 and high-/low-risk-cohort. Our study identified 15 prognosis-related genes of MIBC, provided a feasible stratification method to help for the future immunotherapy strategies of MIBC patients.

Screening ANLN and ASPM as bladder urothelial carcinoma-related biomarkers based on weighted gene co-expression network analysis

“…The correlation was higher in paracancerous tissues, indicating that the interaction between ANLN and ASPM also exists in normal tissues. Previous studies have confirmed ANLN and ASPM as risk factors for the prognosis of patients with BLCA through silico data analysis (Chen et al, 2019;Wang et al, 2019;Xu et al, 2019;Li et al, 2020;Liu et al, 2021b). Our study aimed to further discuss the impact of these genes on BLCA.…”

A risk signature based on necroptotic-process-related genes predicts prognosis and immune therapy response in kidney cell carcinoma

“…Then, the single-sample gene set enrichment (ssGSEA) method in GSVA R-package was carried out to quantitate the infiltration levels of these gene sets. The ssGSEA score of individual immune cell types was standardized by the equation of our previous study (17). The proportion of 22 immune cell types for an individual sample was computed by Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT).…”