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全面泛癌分析揭示 CD70 是透明细胞肾细胞癌中有前景的治疗靶点与生物标志物

英文原题:Comprehensive pan-cancer analysis reveals CD70 as a promising therapeutic target and biomarker in clear cell renal cell carcinoma.

PubMed 2025/03/18(内容时间) Int J Biol Macromol Q1 · IF 8.7(JCR 2025)

研究概要

CD70 是肿瘤坏死因子家族的成员,已被认为与肿瘤发生相关的多种细胞过程有关。

中文摘要

肿瘤坏死因子家族成员 CD70 参与多种与肿瘤发生相关的细胞过程。尽管已知 CD70 在某些癌症中表达,但尚无对其进行全面泛癌分析并在透明细胞肾细胞癌(ccRCC)中开展功能验证的研究。研究者利用公开数据库开展泛癌分析,考察 CD70 在多种癌症中的表达和预后意义。为进行功能验证,研究者对 ccRCC 及邻近正常组织进行免疫组织化学检测,评估 CD70 表达水平。此外,还建立 ccRCC 类器官模型,并开展 CAR-T 细胞细胞毒性试验,评估体外靶向 CD70 的效果。泛癌分析显示,若干癌种中 CD70 表达升高,包括 ccRCC;在 ccRCC 中,CD70 高表达与不良预后相关。免疫组织化学分析证实,ccRCC 组织中 CD70 表达显著高于正常组织。在 ccRCC 类器官模型中,靶向 CD70 的 CAR-T 细胞可有效杀伤 CD70 表达阳性的类器官。CD70 在多种癌症中的高表达凸显其作为通用生物标志物的潜力。重要的是,研究结果强调 CD70 是 ccRCC 中具有临床意义的关键致癌因子和有前景的治疗靶点,并对推进个体化医疗具有启示。

展开英文摘要原文

CD70, a member of the tumor necrosis factor family, has been implicated in various cellular processes associated with tumorigenesis. Despite its known expression in certain cancers, a detailed pan-cancer analysis and functional validation in clear cell renal cell carcinoma (ccRCC) have not been comprehensively explored. We conducted a pan-cancer analysis using publicly available databases to investigate the expression and prognostic significance of CD70 across various cancer types. For functional validation, immunohistochemistry was performed on ccRCC and adjacent normal tissues to evaluate CD70 expression levels. Additionally, ccRCC organoid model was developed and subjected to CAR-T cell cytotoxicity assays to evaluate the efficacy of targeting CD70 in vitro. The pan-cancer analysis revealed elevated expression of CD70 in several cancer types, including ccRCC, where it correlated with poor prognosis. Immunohistochemical analysis confirmed significant overexpression of CD70 in ccRCC tissues compared to normal tissues. In the ccRCC organoid model, CAR-T cells targeting CD70 demonstrated effective cytotoxicity against organoids expressing CD70. The overexpression of CD70 across diverse cancer types underscores its potential as a universal biomarker. Importantly, our findings underscore the clinical relevance of CD70 as a critical oncogenic factor and a promising therapeutic target in ccRCC, with implications for advancing personalized medicine.

论文信息

作者
Zhang X、Hong B、Yu W、Miao Q、Wang W、Wang Y、Sun Z、Bo Y
第一作者单位
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.China
通讯作者单位
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. Electronic address: Azurology_zn@126.com.China
期刊
International journal of biological macromolecules2025 May
原文标识
PubMed 40113005 · DOI 10.1016/j.ijbiomac.2025.142079