Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
Inflamm Res. 2023 Aug;72(8):1665-1687. doi: 10.1007/s00011-023-01772-6. Epub 2023 Aug 14.
To identify CD8 T cell-related molecular clusters and establish a novel gene signature for predicting the prognosis and efficacy of immunotherapy in bladder cancer (BCa).
Transcriptome and clinical data of BCa samples were obtained from the Cancer Genome Atlas (TCGA) and GEO databases. The CD8 T cell-related genes were screened through the CIBERSORT algorithm and correlation analysis. Consensus clustering analysis was utilized to identified CD8 T cell-related molecular clusters. A novel CD8 T cell-related prognostic model was developed using univariate Cox regression analysis and Lasso regression analysis. Internal and external validations were performed and the validity of the model was validated in a real-world cohort. Finally, preliminary experimental verifications were carried out to verify the biological functions of SH2D2A in bladder cancer.
A total of 52 CD8 T cell-related prognostic genes were screened and two molecular clusters with notably diverse immune cell infiltration, prognosis and clinical features were developed. Then, a novel CD8 T cell-related prognostic model was constructed. The patients with high-risk scores exhibited a significantly worse overall survival in training, test, whole TCGA and validating cohort. The AUC was 0.766, 0.725, 0.739 and 0.658 in the four cohorts sequentially. Subgroup analysis suggested that the novel prognostic model has a robust clinical application for selecting high-risk patients. Finally, we confirmed that patients in the low-risk group might benefit more from immunotherapy or chemotherapy, and validated the prognostic model in a real-world immunotherapy cohort. Preliminary experiment showed that SH2D2A was capable of attenuating proliferation, migration and invasion of BCa cells.
CD8 T cell-related molecular clusters were successfully identified. Besides, a novel CD8 T cell-related prognostic model with an excellent predictive performance in predicting survival rates and immunotherapy efficacy of BCa was developed.
鉴定 CD8 T 细胞相关分子簇，并建立一种新的基因特征，以预测膀胱癌（BCa）免疫治疗的预后和疗效。
从癌症基因组图谱（TCGA）和 GEO 数据库中获取 BCa 样本的转录组和临床数据。通过 CIBERSORT 算法和相关性分析筛选 CD8 T 细胞相关基因。采用共识聚类分析鉴定 CD8 T 细胞相关分子簇。采用单因素 Cox 回归分析和 Lasso 回归分析建立新的 CD8 T 细胞相关预后模型。进行内部和外部验证，并在真实队列中验证模型的有效性。最后，进行初步的实验验证，以验证 SH2D2A 在膀胱癌中的生物学功能。
筛选出 52 个与 CD8 T 细胞相关的预后基因，构建了两个具有显著不同免疫细胞浸润、预后和临床特征的分子簇。然后，构建了一个新的 CD8 T 细胞相关预后模型。在训练、测试、整个 TCGA 和验证队列中，高风险评分患者的总生存期明显较差。AUC 分别为 0.766、0.725、0.739 和 0.658。亚组分析表明，该新预后模型在选择高危患者方面具有较强的临床应用价值。最后，我们证实低风险组的患者可能从免疫治疗或化疗中获益更多，并在真实世界的免疫治疗队列中验证了该预后模型。初步实验表明，SH2D2A 能够减弱膀胱癌细胞的增殖、迁移和侵袭。
成功鉴定了 CD8 T 细胞相关分子簇。此外，还建立了一种新的 CD8 T 细胞相关预后模型，该模型在预测 BCa 生存率和免疫治疗疗效方面具有优异的预测性能。
