研究动态
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开发用于肝细胞癌预后评估的新型 CD8 T 细胞相关特征。

Development of a Novel CD8+ T Cell-Associated Signature for Prognostic Assessment in Hepatocellular Carcinoma.

发表日期:2024
作者: Xuezhi Li, Xiaodong Qu, Songbo Li, Kexin Lin, Nuo Yao, Na Wang, Yongquan Shi
来源: GENES & DEVELOPMENT

摘要:

本研究旨在分析CD8 T细胞相关调控基因在肝细胞癌(HCC)中的临床意义和预后价值。这是一项回顾性研究。我们结合 TCGA-LIHC 和单细胞 RNA 测序数据进行 Lasso-Cox 回归分析,筛选 CD8 T 细胞相关基因,构建新的特征。使用 qRT-PCR、免疫组织化学和组织微阵列在细胞和组织水平检测特征基因的表达。然后使用 CIBERSORT 算法评估不同风险组之间的免疫微环境差异,并进行药物敏感性分析以筛选潜在的 HCC 治疗药物。 8 基因 CD8 T 细胞相关特征(FABP5、GZMH、ANXA2、KLRB1) 、CD7、IL7R、BATF 和 RGS2)被构建。生存分析显示,所有队列中高危患者的预后均较差。肿瘤免疫微环境分析显示,22种免疫细胞类型在不同风险组患者之间存在显着差异,低风险组患者的免疫系统在免疫功能方面更为活跃。高危组患者更容易发生免疫逃逸,对免疫治疗的反应较差,AZD7762被筛选为高危组中最敏感的药物。最后,初步实验表明,BATF对HuH-7细胞的增殖、迁移和侵袭具有促进作用。CD8 T细胞相关特征有望成为优化个体患者决策和监测方案的工具,为HCC的治疗和预后评估提供新思路。
The aim of this study was to analyze the clinical significance and prognostic value of CD8+ T cell-related regulatory genes in hepatocellular carcinoma (HCC).This was a retrospective study. We combined TCGA-LIHC and single-cell RNA sequencing data for Lasso-Cox regression analysis to screen for CD8+ T cell-associated genes to construct a novel signature. The expression of the signature genes was detected at cellular and tissue levels using qRT-PCR, immunohistochemistry, and tissue microarrays. The CIBERSORT algorithm was then used to assess the immune microenvironmental differences between the different risk groups and a drug sensitivity analysis was performed to screen for potential HCC therapeutic agents.An 8-gene CD8 + T cell-associated signature (FABP5, GZMH, ANXA2, KLRB1, CD7, IL7R, BATF, and RGS2) was constructed. Survival analysis showed that high-risk patients had a poorer prognosis in all cohorts. Tumor immune microenvironment analysis revealed 22 immune cell types that differed significantly between patients in different risk groups, with patients in the low-risk group having an immune system that was more active in terms of immune function. Patients in the high-risk group were more prone to immune escape and had a poorer response to immunotherapy, and AZD7762 was screened as the most sensitive drug in the high-risk group. Finally, preliminary experiments have shown that BATF has a promoting effect on the proliferation, migration and invasion of HuH-7 cells.The CD8+ T-cell-associated signature is expected to be a tool for optimizing individual patient decision-making and monitoring protocols, and to provide new ideas for treatment and prognostic assessment of HCC.