Song Xiaojie, Zhao Guanghui, Wang Guangqiang, Gao Haidong
Department of Respiratory and Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, China.
Medical Laboratory Center, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao 266035, China.
Cancers (Basel). 2022 Oct 22;14(21):5183. doi: 10.3390/cancers14215183.
CD8+ T cells infiltrating the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) are critical for establishing antitumor immunity. Nevertheless, the global landscape of their numbers, functional status, and differentiation trajectories remains unclear. In the single-cell RNA-sequencing (scRNA-seq) dataset GSE131907 of LUAD, the CD8+T cells were selected for TSNE clustering, and the results showed that they could be divided into ten subsets. The cell differentiation trajectory showed the presence of abundant transition-state CD8+ T cells during the differentiation of naive-like CD8+ T cells into cytotoxic CD8+ T cells and exhausted CD8+ T cells. The differentially expressed marker genes among subsets were used to construct the gene signature matrix, and the proportion of each subset was identified and calculated in The Cancer Genome Atlas (TCGA) samples. Survival analysis showed that the higher the proportion of the exhausted CD8+ T lymphocyte (ETL) subset, the shorter the overall survival (OS) time of LUAD patients ( = 0.0098). A total of 61 genes were obtained by intersecting the differentially expressed genes (DEGs) of the ETL subset, and the DEGs of the TCGA samples were divided into a high and a low group according to the proportion of the ETL subset. Through protein interaction network analysis and survival analysis, four hub genes that can significantly affect the prognosis of LUAD patients were finally screened, and RT-qPCR and Western blot verified the differential expression of the above four genes. Our study further deepens the understanding of the heterogeneity and functional exhaustion of infiltrating CD8+ T cells in LUAD. The screened prognostic marker genes provide potential targets for targeted therapy and immunotherapy in LUAD patients.
浸润肺腺癌（LUAD）肿瘤微环境（TME）的CD8 + T细胞对于建立抗肿瘤免疫至关重要。然而，它们的数量、功能状态和分化轨迹的整体情况仍不清楚。在LUAD的单细胞RNA测序（scRNA-seq）数据集GSE131907中，选择CD8 + T细胞进行TSNE聚类，结果表明它们可分为十个亚群。细胞分化轨迹显示，在幼稚样CD8 + T细胞向细胞毒性CD8 + T细胞和耗竭性CD8 + T细胞分化过程中存在大量过渡态CD8 + T细胞。利用亚群间差异表达的标记基因构建基因特征矩阵，并在癌症基因组图谱（TCGA）样本中识别和计算每个亚群的比例。生存分析表明，耗竭性CD8 + T淋巴细胞（ETL）亚群的比例越高，LUAD患者的总生存（OS）时间越短（P = 0.0098）。通过对ETL亚群差异表达基因（DEG）进行交集分析，共获得61个基因，并根据ETL亚群的比例将TCGA样本的DEG分为高、低两组。通过蛋白质相互作用网络分析和生存分析，最终筛选出四个可显著影响LUAD患者预后的枢纽基因，RT-qPCR和Western blot验证了上述四个基因的差异表达。我们的研究进一步加深了对LUAD中浸润性CD8 + T细胞异质性和功能耗竭的理解。筛选出的预后标志物基因为LUAD患者的靶向治疗和免疫治疗提供了潜在靶点。
