Abstract
Compelling evidence indicates that immune function is correlated with the prognosis of bladder cancer (BC). Here, we aimed to develop a clinically translatable immune-related gene pairs (IRGPs) prognostic signature to estimate the overall survival (OS) of bladder cancer. From the 251 prognostic-related IRGPs, 37 prognostic-related IRGPs were identified using LASSO regression. We identified IRGPs with the potential to be prognostic markers. The established risk scores divided BC patients into high and low risk score groups, and the survival analysis showed that risk score was related to OS in the TCGA-training set (p < 0.001; HR = 7.5 [5.3, 10]). ROC curve analysis showed that the AUC for the 1-year, 3-year, and 5-year follow-up was 0.820, 0.883, and 0.879, respectively. The model was verified in the TCGA-testing set and external dataset GSE13507. Multivariate analysis showed that risk score was an independent prognostic predictor in patients with BC. In addition, significant differences were found in gene mutations, copy number variations, and gene expression levels in patients with BC between the high and low risk score groups. Gene set enrichment analysis showed that, in the high-risk score group, multiple immune-related pathways were inhibited, and multiple mesenchymal phenotype-related pathways were activated. Immune infiltration analysis revealed that immune cells associated with poor prognosis of BC were upregulated in the high-risk score group, whereas immune cells associated with a better prognosis of BC were downregulated in the high-risk score group. Other immunoregulatory genes were also differentially expressed between high and low risk score groups. A 37 IRGPs-based risk score signature is presented in this study. This signature can efficiently classify BC patients into high and low risk score groups. This signature can be exploited to select high-risk BC patients for more targeted treatment.
Highlights
Bladder cancer is the most common malignant tumor of the urinary system with high morbidity and mortality [1]
We retrieved 1,811 unique immune-related genes from the ImmPort database, of which 1,223 IRGs were shared between the TCGA and GSE13507 datasets. en, we constructed 1495729 immune-related gene pairs (IRGPs) using unique 1223 immune genes
We used the cox proportional hazards regression model and survival analysis to screen the IRGPs related to prognosis among the differentially expressed IRGPs
Summary
Bladder cancer is the most common malignant tumor of the urinary system with high morbidity and mortality [1]. In 2020, there would be approximately 81,400 new cases of bladder cancer cases and more than 17,980 deaths due to kidney cancer in the United States [2]. At the time of initial diagnosis, approximately 75% of bladder cancer patients are non-muscle invasive bladder cancer (NMIBC), and about 25% of the patients are muscle infiltrating bladder cancer (MIBC), or metastatic disease [3, 4]. Most NMIBC relapses within 6–12 months, and 10%–15% of patients may progress to invasive or metastatic disease [5]. The 5-year survival rate of bladder cancer at all stages does not exceed 20% [6]
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