Construction of a prognostic model based on CD8+ T cell exhaustion-related gene set and investigation of the tumor immune microenvironment
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Abstract:
[Abstract] Objective: To construct a prognostic model across multiple cancer types based on exhausted T cell (Tex) gene sets and to identify novel Tex cell markers. Methods: A pan-cancer single-cell dataset of CD8+ T cells was utilized to identify the pan-cancer Tex gene set. Differential expression analysis and Cox regression analysis of TCGA data were performed to screen pan-cancer prognostic genes. These genes were then intersected with the Tex gene set, yielding a pan-cancer Tex prognostic gene set. Cox regression analysis was used to construct a pan-cancer prognostic model, and the model's performance was evaluated using Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve analyses. In addition, correlation analysis was further applied to explore the role of TNFRSF18 in immunotherapy. Results: Cox regression analysis identified CXCL13, CDKN2A, TNFRSF18, and IL2RA as key prognostic genes, on which the prognostic model was constructed. Survival analysis showed that patients in the low-risk group exhibited significantly higher survival rates across various cancer types (P < 0.05). Single-cell data analysis demonstrated that TNFRSF18 was specifically expressed in Tex cells and was significantly upregulated in tumor samples from various cancers (P < 0.05). Conclusion: The pan-cancer Tex cell-based prognostic model showed robust predictive performance across various cancers. TNFRSF18 may function as a novel potential biomarker of Tex cells and play a role in cancer immunotherapy.