Yan Ting, Zhou Wei, Li Chun
Department of Blood Purification Center, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, No.141, Tianjin Road, Huangshi, 435000, Hubei, People's Republic of China.
Department of Urology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, People's Republic of China.
Int Urol Nephrol. 2024 Nov;56(11):3447-3462. doi: 10.1007/s11255-024-04086-6. Epub 2024 May 24.
BACKGROUND: The efficacy of immunotherapy is heavily influenced by T cell activity. This study aimed to examine how T cell proliferation regulators can predict the prognosis and response to immunotherapy in patients with bladder cancer (BCa). METHODS: T cell proliferation-related subtypes were determined by employing the non-negative matrix factorization (NMF) algorithm that analyzed the expression patterns of T cell proliferation regulators. Subtypes were assessed for variations in prognosis, immune infiltration, and functional behaviors. Subsequently, a risk model related to T cell proliferation was created through Cox and Lasso regression analyses in the TCGA cohort and then confirmed in two GEO cohorts and an immunotherapy cohort. RESULTS: BCa patients were categorized into two subtypes (C1 and C2) according to the expression profiles of 31 T cell proliferation-related genes (TRGs) with distinct prognoses and immune landscapes. The C2 subtype had a shorter overall survival (OS), with higher levels of M2 macrophage infiltration, and the activation of cancer-related pathways than the C1 subtype. Following this, thirteen prognosis-related genes that were involved in T cell proliferation were utilized to create the prognostic signature. The model's predictive accuracy was confirmed by analyzing both internal and external datasets. Individuals in the high-risk category experienced a poorer prognosis, increased immunosuppressive factors in the tumor microenvironment, and diminished responses to immunotherapy. Additionally, the immunotherapeutic prediction efficacy of the model was further confirmed by an immunotherapy cohort (anti-PD-L1 in the IMvigor210 cohort). CONCLUSIONS: Our study characterized two subtypes linked to T cell proliferation in BCa patients with distinct prognoses and tumor microenvironment (TME) patterns, providing new insights into the heterogeneity of T cell proliferation in BCa and its connection to the immune landscape. The signature has prospective clinical implications for predicting outcomes and may help physicians to select prospective responders who prioritize current immunotherapy.
背景:免疫疗法的疗效受T细胞活性的严重影响。本研究旨在探讨T细胞增殖调节因子如何预测膀胱癌(BCa)患者的预后及对免疫疗法的反应。 方法:采用非负矩阵分解(NMF)算法确定T细胞增殖相关亚型,该算法分析T细胞增殖调节因子的表达模式。评估亚型在预后、免疫浸润和功能行为方面的差异。随后,通过Cox和Lasso回归分析在TCGA队列中建立与T细胞增殖相关的风险模型,然后在两个GEO队列和一个免疫疗法队列中进行验证。 结果:根据31个T细胞增殖相关基因(TRGs)的表达谱,将BCa患者分为两个亚型(C1和C2),其预后和免疫格局不同。与C1亚型相比,C2亚型的总生存期(OS)较短,M2巨噬细胞浸润水平较高,且癌症相关通路激活程度更高。在此基础上,利用13个参与T细胞增殖的预后相关基因创建预后特征。通过分析内部和外部数据集证实了该模型的预测准确性。高危组个体的预后较差,肿瘤微环境中的免疫抑制因子增加,对免疫疗法的反应减弱。此外,免疫疗法队列(IMvigor210队列中的抗PD-L1)进一步证实了该模型的免疫治疗预测效能。 结论:我们的研究对BCa患者中与T细胞增殖相关的两个亚型进行了特征描述,其预后和肿瘤微环境(TME)模式不同,为BCa中T细胞增殖的异质性及其与免疫格局的关系提供了新的见解。该特征对预测结果具有前瞻性临床意义,可能有助于医生选择优先接受当前免疫疗法的潜在反应者。
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