The First Clinical Medical College, Lanzhou University, Lanzhou, China.
The Second Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
IET Syst Biol. 2023 Aug;17(4):228-244. doi: 10.1049/syb2.12072. Epub 2023 Jul 11.
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.
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。