[摘 要] 目的：本研究旨在基于耗竭T细胞（Tex细胞）基因集构建一个针对多种肿瘤的预后模型，同时挖掘新型Tex细胞标志 物。方法：利用CD8+ T细胞的泛癌单细胞数据集鉴定出泛癌Tex细胞基因集。通过对TCGA数据库中数据进行差异表达分析 与Cox回归分析，得到泛癌预后基因，并与Tex细胞基因集取交集，筛选出泛癌Tex细胞预后基因集。运用Cox回归分析来构建 泛癌预后模型，并采用Kaplan-Meier生存曲线及受试者工作特征曲线（ROC）来评估模型效果。此外，采用相关性分析进一步探 究肿瘤坏死因子受体超家族成员18（TNFRSF18）在免疫治疗中的作用。结果：通过Cox回归分析，选定CXCL13、CDKN2A、 TNFRSF18和IL2RA为关键预后相关基因，并基于此结果来构建预后模型。生存曲线分析结果显示，低风险组患者在多种 肿瘤中，表现出更高的生存率（P < 0.05）。单细胞数据分析发现TNFRSF18在Tex细胞中呈现特异性表达，且在多种肿瘤样本 中，该基因呈显著上调（P < 0.05）。结论：泛癌Tex细胞预后模型在多种肿瘤中，均表现出良好的预测性能。TNFRSF18作为潜 在的新型Tex细胞生物标志物，可能在肿瘤免疫治疗中发挥作用。

[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.

[基金项目] 江苏省自然基金项目（No. BK20220279）；姑苏创新创业领 军人才计划（No. ZXL2022475）