单细胞 RNA 测序和批量 RNA 测序探索耗竭 T 细胞在肝细胞癌中的预后价值。

Single-cell RNA-seq and bulk RNA-seq explore the prognostic value of exhausted T cells in hepatocellular carcinoma.

机构信息

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

The Second Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

出版信息

IET Syst Biol. 2023 Aug;17(4):228-244. doi: 10.1049/syb2.12072. Epub 2023 Jul 11.

Abstract

Hepatocellular carcinoma (HCC) remains a worldwide health problem. Mounting evidence indicates that exhausted T cells play a critical role in the progress and treatment of HCC. Therefore, a detailed characterisation of exhausted T cells and their clinical significance warrants further investigation in HCC. Based on the GSE146115, we presented a comprehensive single-cell Atlas in HCC. Pseudo-time analysis revealed that tumour heterogeneity progressively increased, and the exhausted T cells gradually appeared during tumour progression. Functional enrichment analysis revealed that the evolutionary process of exhausted T cells mainly contained the pathway of cadherin binding, proteasome, cell cycle, and T cell receptor regulation of apoptosis. In the International Cancer Genome Consortium database, we divided patients into three clusters with the T cell evolution-associated genes. We found that the exhausted T cells are significantly related to poor outcomes through immunity and survival analysis. In The Cancer Genome Atlas database, the authors enrolled weighted gene co-expression network analysis, univariate Cox analysis, and Lasso Cox analysis, then screened the 19 core genes in T cells evolution and built a robust prognostic model. This study offers a fresh view on evaluating the patients' outcomes from an exhausted T cells perspective and might help clinicians develop therapeutic systems.

摘要

肝细胞癌 (HCC) 仍然是一个全球性的健康问题。越来越多的证据表明,耗竭的 T 细胞在 HCC 的进展和治疗中起着关键作用。因此,详细描述耗竭的 T 细胞及其临床意义值得在 HCC 中进一步研究。基于 GSE146115,我们在 HCC 中呈现了一个全面的单细胞图谱。伪时间分析表明肿瘤异质性逐渐增加,耗竭的 T 细胞在肿瘤进展过程中逐渐出现。功能富集分析表明,耗竭的 T 细胞的进化过程主要包含钙粘蛋白结合、蛋白酶体、细胞周期和 T 细胞受体凋亡调节途径。在国际癌症基因组联合会数据库中,我们根据 T 细胞进化相关基因将患者分为三个簇。我们通过免疫和生存分析发现,耗竭的 T 细胞与不良预后显著相关。在癌症基因组图谱数据库中,作者进行了加权基因共表达网络分析、单变量 Cox 分析和 Lasso Cox 分析,然后筛选出 T 细胞进化中的 19 个核心基因,并构建了一个稳健的预后模型。这项研究从耗竭的 T 细胞的角度提供了一种评估患者预后的新视角,并可能有助于临床医生开发治疗系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62c5/10439497/5db0a2cc83e7/SYB2-17-228-g002.jpg

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