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基于多组学数据的 B7 家族免疫预后、免疫浸润和免疫治疗反应的综合泛癌评估。

An integrated pan-cancer assessment of prognosis, immune infiltration, and immunotherapy response for B7 family using multi-omics data.

机构信息

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

出版信息

Life Sci. 2024 Sep 15;353:122919. doi: 10.1016/j.lfs.2024.122919. Epub 2024 Jul 19.

Abstract

AIMS

B7 molecules (B7s) are crucial synergistic signals for effective immune surveillance against tumor cells. While previous studies have explored the association between the B7 family and cancer, most have been limited to specific genes or cancer subtypes.

MAIN METHODS

Our study utilized multi-omics data to investigate potential correlations between B7s expression (B7s exp.) and prognosis, clinicopathological features, somatic mutations (SMs), copy number variations (CNVs), immune characteristics, tumor microenvironment (TME), microsatellite instability, tumor mutation burden, immune checkpoint gene (ICG), and drug responsiveness in TCGA tumors. Furthermore, the connection between B7s exp. and immunotherapy (IT) performance assessed in various validated datasets. Following this, immune infiltration analysis (IIA) was conducted based on B7s exp., CNVs, or SMs in bladder cancer (BLCA), complemented by real-time PCR (RT-PCR) and protein confirmation of B7-H3.

KEY FINDINGS

Across most cancer types, B7s exp. was related to prognosis, clinicopathological characteristics, mutations, CNVs, ICG, TMB, TME. The examination of sensitivity to anticancer drugs unveiled correlations between B7 molecules and different drug sensitivities. Specific B7s exp. patterns were linked to the clinical effectiveness of IT. Using GSEA, several enriched immune-related functions and pathways were identified. Particularly in BLCA, IIA revealed significant connections between B7 CNVs, mutation status, and various immune cell infiltrates. RT-PCR confirmed elevated B7-H3 gene levels in BLCA tumor tissues.

SIGNIFICANCE

This study confirmed the significance of B7s exp. and genomic changes in predicting outcomes and treatment across different cancer types. Moreover, they indicate a critical function of B7s in BLCA and their potential as IT biomarkers.

摘要

目的

B7 分子(B7s)是针对肿瘤细胞进行有效免疫监视的关键协同信号。虽然先前的研究已经探讨了 B7 家族与癌症之间的关联,但大多数研究都局限于特定的基因或癌症亚型。

主要方法

我们的研究利用多组学数据来研究 B7s 表达(B7s exp.)与预后、临床病理特征、体细胞突变(SMs)、拷贝数变异(CNVs)、免疫特征、肿瘤微环境(TME)、微卫星不稳定性、肿瘤突变负担、免疫检查点基因(ICG)和 TCGA 肿瘤对药物反应之间的潜在相关性。此外,还评估了 B7s exp. 在各种验证数据集的免疫治疗(IT)中的作用。之后,我们根据膀胱癌(BLCA)中的 B7s exp.、CNVs 或 SMs 进行免疫浸润分析(IIA),并通过实时 PCR(RT-PCR)和 B7-H3 蛋白验证进行补充。

主要发现

在大多数癌症类型中,B7s exp. 与预后、临床病理特征、突变、CNVs、ICG、TMB、TME 相关。对抗癌药物敏感性的检查揭示了 B7 分子与不同药物敏感性之间的相关性。特定的 B7s exp. 模式与 IT 的临床疗效相关。通过 GSEA,发现了几个丰富的免疫相关功能和途径。特别是在 BLCA 中,IIA 揭示了 B7 CNVs、突变状态与各种免疫细胞浸润之间的显著联系。RT-PCR 证实 BLCA 肿瘤组织中 B7-H3 基因水平升高。

意义

本研究证实了 B7s exp. 和基因组变化在预测不同癌症类型的结局和治疗中的重要性。此外,它们表明 B7s 在 BLCA 中的关键作用及其作为 IT 生物标志物的潜力。

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