基于单细胞RNA测序和批量RNA测序数据鉴定与甲状腺乳头状癌中T细胞增殖相关的预后基因
Identification of prognostic genes related to T cell proliferation in papillary thyroid cancer based on single-cell RNA sequencing and bulk RNA sequencing data.
作者信息
Meng Qingkai, Liu Hongzhu, Wang Mengtong, Jiang Xin, Wang Yi, Cao Xiaoli, Qu Nina
机构信息
School of Medical Imaging, Binzhou Medical University, Yantai, 264003, Shandong, China.
Shandong Second Medical University, Weifang, 264000, Shandong, China.
出版信息
Clin Exp Med. 2025 Aug 2;25(1):273. doi: 10.1007/s10238-025-01826-5.
Papillary thyroid carcinoma (PTC) is the main pathological subtype of thyroid cancer. Given the strong association between T cells and PTC, this study focused on the prognostic value and potential molecular mechanisms of T cell proliferation-related genes (TPRGs) in PTC. ScRNA-seq data were analyzed to identify key cells and subpopulations based on public databases. Candidate genes were determined by intersecting differentially expressed genes (DEGs) from differential expression analysis of key subpopulations, high- and low-TPRGs score groups, and bulk RNA-seq data. Prognostic genes were then determined via Cox regression and a machine learning algorithm. A risk model was formed. PTC patients were grouped into high-risk and low-risk groups by risk score. Subsequently, the immune microenvironment was analyzed. Finally, cell communication analysis and pseudotime analysis were accomplished. T/NK cells were selected as key cells. Moreover, CD4 memory cells were selected as the key subpopulation. Meanwhile, KLRB1, TSHZ2, and TRABD2A were spotted as prognostic genes. The risk model had better prognostic value. Additionally, 5 DICs were spotted in two risk groups. Besides, the scores of IPS-CTLA4 and PD-L1 blocker, IPS-CTLA4 blocker, and IPS-PD-1 blocker were lower in the HRG group. In addition, the most substantial receptor-ligand interaction in T/NK cells was found to be CLEC2C-KLRB1. Moreover, as T/NK cells differentiated, the expression level of KLRB1 was observed to rise slowly at first and then decline rapidly. KLRB1, TSHZ2, and TRABD2A were spotted as prognostic genes, providing new PTC prognosis and treatment strategies.
甲状腺乳头状癌(PTC)是甲状腺癌的主要病理亚型。鉴于T细胞与PTC之间的密切关联,本研究聚焦于PTC中T细胞增殖相关基因(TPRGs)的预后价值及潜在分子机制。基于公共数据库分析单细胞RNA测序(scRNA-seq)数据以识别关键细胞和亚群。通过对关键亚群、高TPRGs评分组和低TPRGs评分组的差异表达分析以及批量RNA测序数据中的差异表达基因(DEGs)进行交叉分析来确定候选基因。然后通过Cox回归和机器学习算法确定预后基因。形成了一个风险模型。根据风险评分将PTC患者分为高风险组和低风险组。随后,分析免疫微环境。最后,完成细胞通讯分析和拟时间分析。选择T/NK细胞作为关键细胞。此外,选择CD4记忆细胞作为关键亚群。同时,发现杀伤细胞凝集素样受体亚家族B成员1(KLRB1)、TSHZ2和TRABD2A为预后基因。该风险模型具有更好的预后价值。此外,在两个风险组中发现了5种细胞间通讯分子(DICs)。此外,高风险组中免疫检查点抑制剂(IPS)-CTLA4和PD-L1阻断剂、IPS-CTLA4阻断剂以及IPS-PD-1阻断剂的评分较低。另外,发现T/NK细胞中最显著的受体-配体相互作用是C型凝集素结构域家族2成员C(CLEC2C)-KLRB1。而且,随着T/NK细胞分化,观察到KLRB1的表达水平起初缓慢上升,然后迅速下降。KLRB1、TSHZ2和TRABD2A被确定为预后基因,为PTC的预后和治疗策略提供了新的思路。