一种基于 γ-δ 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帮助治疗。
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.
发表日期:2024 May 25
作者:
Yaqian Wu, Mengfei Yao, Zonglong Wu, Lulin Ma, Cheng Liu
来源:
GENES & DEVELOPMENT
摘要:
ccRCC 是 RCC 的主要形式,占大多数病例。癌症的形成和人体对抗肿瘤的能力与γδT细胞密切相关。我们检查并分析了535名被诊断患有ccRCC的个体和72名对照个体的基因表达模式,全部来自TCGA -KIRC数据集,随后通过分子生物学实验验证。在ccRCC中,我们发现了304个模块基因(DEGRG),这些基因差异表达并与γδ T细胞相关。使用通过单变量 Cox 和 LASSO 回归分析确定的 13 个差异 DEGRG 构建了 ccRCC 风险模型,这些差异与预后相关。该风险模型在训练和验证数据集中都表现出了出色的性能。高危组和低危组之间免疫检查点抑制剂和肿瘤免疫微环境的比较表明,免疫治疗可以为低危患者带来积极的结果。此外,在敲除与不同类型癌症相关的基因 TMSB10 后,在细胞培养物中观察到 ccRCC 细胞增殖、迁移和侵袭的抑制。 总之,我们使用以 γδ T 为中心的风险模型创建了精确的预测生物标志物细胞,可以预测临床结果并为创新靶向疗法的进展提供方向。© 2024。作者。
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.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.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.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.© 2024. The Author(s).