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一种基于γδ T 细胞的新预后模型,用于预测透明细胞肾细胞癌的风险并辅助治疗

英文原题:A new prognostic model based on gamma-delta T cells for predicting the risk and aiding in the treatment of clear cell renal cell carcinoma.

查看英文原题

A new prognostic model based on gamma-delta T cells for predicting the risk and aiding in the treatment of clear cell renal cell carcinoma.

PubMed 2024/05/25(内容时间) Discov Oncol Q3 · IF 2.8(JCR 2025)

研究概要

我们利用以γδ T细胞为核心的风险模型,构建了一种精确的预测性生物标志物,能够预测临床结果并为创新靶向疗法的进展提供方向。

研究思路结论见上方概要

ccRCC是RCC的主要形式,占大多数病例。癌症的形成与机体抗肿瘤能力与γδ T细胞密切相关。

我们检查并分析了535名诊断为ccRCC的个体和72名作为对照的个体的基因表达模式,所有样本均来源于TCGA-KIRC数据集,随后通过分子生物学实验进行了验证。

在ccRCC中,我们发现了304个差异表达且与γδ T细胞相关的模块基因(DEGRGs)。通过单因素Cox和LASSO回归分析鉴定出13个与预后相关的差异DEGRGs,并以此构建了ccRCC的风险模型。该风险模型在训练集和验证集中均表现出色。高风险组与低风险组之间免疫检查点抑制剂和肿瘤免疫微环境的比较表明,免疫治疗可能对低风险患者产生积极结果。此外,在细胞培养中敲低TMSB10(一种与多种癌症相关的基因)后,观察到ccRCC细胞增殖、迁移和侵袭受到抑制。

展开英文摘要原文

BACKGROUND: ccRCC is the prevailing form of RCC, accounting for the majority of cases. The formation of cancer and the body's ability to fight against tumors are strongly connected to Gamma delta (γδ) T cells. METHODS: We examined and analyzed the gene expression patterns of 535 individuals diagnosed with ccRCC and 72 individuals serving as controls, all sourced from the TCGA-KIRC dataset, which were subsequently validated through molecular biology experiments. RESULTS: In ccRCC, we discovered 304 module genes (DEGRGs) that were ex-pressed differentially and linked to γδ T cells. A risk model for ccRCC was constructed using 13 differentially DEGRGs identified through univariate Cox and LASSO regression analyses, which were found to be associated with prognosis. The risk model exhibited outstanding performance in both the training and validation datasets. The comparison of immune checkpoint inhibitors and the tumor immune microenvironment between the high- and low-risk groups indicates that immunotherapy could lead to positive results for low-risk patients. Moreover, the inhibition of ccRCC cell proliferation, migration, and invasion was observed in cell culture upon knocking down TMSB10, a gene associated with different types of cancers. CONCLUSIONS: In summary, we have created a precise predictive biomarker using a risk model centered on γδ T cells, which can anticipate clinical results and provide direction for the advancement of innovative targeted therapies.

论文信息

作者
Wu Y、Yao M、Wu Z、Ma L、Liu C
第一作者单位
Department of Urology, Peking University Third Hospital, Beijing, 100191, People's Republic of China.China
通讯作者单位
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China. chengliu@bjmu.edu.cn.China
期刊
Discover oncology2024 May 25
原文标识
PubMed 38795225 · DOI 10.1007/s12672-024-01057-2