Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Nanchang, Nanchang, 330000, China.
Emergency and Trauma Center, The First Hospital of Nanchang, Nanchang, 330000, China.
Funct Integr Genomics. 2023 Aug 2;23(3):259. doi: 10.1007/s10142-023-01188-9.
Colorectal cancer (CRC) remains a significant global health issue. In this study, the role of T-cell exhaustion-related genes (TEXs) in CRC was investigated using single-cell and bulk RNA-seq analysis. This research involved extensive data analysis using multiple databases, including the TCGA-COAD cohort, GSE14333, and GSE39582. Through single-cell analysis, distinct cell populations within CRC samples were identified and classified T-cells into four subgroups: regulatory T-cells (Tregs), conventional CD4+ T-cells (CD4+ T conv), CD8+ T, and CD8+ T exhausted cells. Intercellular communication networks and signaling pathways associated with TEXs using computational tools such as CellChat and PROGENy. Additionally, TEX-related alterations in tumor gene pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Prognostic models were developed, and their correlation with immune infiltration was assessed. The study revealed the presence of distinct cell populations within CRC, with TEXs playing a crucial role in the tumor microenvironment. CD8+ T exhausted cells exhibited expression of specific markers, indicating their involvement in tumor immune evasion. CellChat and PROGENy analyses revealed intricate communication networks and signaling pathways associated with TEXs, including RNA splicing and viral carcinogenesis. Furthermore, the prognostic risk model developed on the basis of TEXs demonstrated its efficacy in stratifying CRC patients. This risk model exhibited strong correlations with immune infiltration by various effector immune cells, highlighting the influence of TEXs on the tumor immune response. The complex interactions and signaling pathways underlying TEX-associated immune dysregulation in CRC were revealed by employing advanced analytical approaches. The development of a prognostic risk model based on TEXs offers a promising tool for prognostic stratification in patients with CRC. Furthermore, the correlations observed between TEXs and immune infiltration provide valuable insights into the potential of TEXs as therapeutic targets and highlight the need for further investigation into TEX-mediated immune evasion mechanisms. This study thus provides valuable insights into the role of TEXs in CRC.
结直肠癌（CRC）仍然是一个重大的全球健康问题。在这项研究中，使用单细胞和批量 RNA-seq 分析研究了 T 细胞耗竭相关基因（TEXs）在 CRC 中的作用。这项研究涉及使用多个数据库（包括 TCGA-COAD 队列、GSE14333 和 GSE39582）进行广泛的数据分析。通过单细胞分析，确定了 CRC 样本中的不同细胞群，并将 T 细胞分为四个亚群：调节性 T 细胞（Tregs）、常规 CD4+T 细胞（CD4+Tconv）、CD8+T 和 CD8+T 耗竭细胞。使用 CellChat 和 PROGENy 等计算工具分析与 TEXs 相关的细胞间通讯网络和信号通路。此外，通过基因本体论和京都基因与基因组百科全书分析分析了肿瘤基因途径中的 TEX 相关改变。开发了预后模型，并评估了它们与免疫浸润的相关性。研究揭示了 CRC 中存在不同的细胞群，TEXs 在肿瘤微环境中起着关键作用。CD8+T 耗竭细胞表达特定标志物，表明它们参与肿瘤免疫逃逸。CellChat 和 PROGENy 分析揭示了与 TEXs 相关的复杂通讯网络和信号通路，包括 RNA 剪接和病毒致癌作用。此外，基于 TEXs 开发的预后风险模型证明了其在 CRC 患者分层中的功效。该风险模型与各种效应免疫细胞的免疫浸润表现出强烈的相关性，突出了 TEXs 对肿瘤免疫反应的影响。通过采用先进的分析方法，揭示了 CRC 中与 TEX 相关的免疫失调的复杂相互作用和信号通路。基于 TEXs 的预后风险模型的开发为 CRC 患者的预后分层提供了一种有前途的工具。此外，观察到的 TEXs 与免疫浸润之间的相关性为 TEXs 作为治疗靶点的潜力提供了有价值的见解，并强调了进一步研究 TEX 介导的免疫逃逸机制的必要性。因此，这项研究为 TEXs 在 CRC 中的作用提供了有价值的见解。
