T cell-related prognostic risk model and tumor immune environment modulation in lung adenocarcinoma based on single-cell and bulk RNA sequencing

免疫系统 核糖核酸 腺癌 肿瘤科 细胞 生物 免疫调节 癌症研究 内科学 计算生物学 医学 癌症 免疫学 基因 遗传学
作者
Jingyuan Zhang,Xinkui Liu,Zhihong Huang,Chao Wu,Fanqin Zhang,Aiqing Han,Antony Stalin,Shan Lu,Siyu Guo,Jiaqi Huang,Pengyun Liu,Rui Shi,Yiyan Zhai,Meilin Chen,Wei Zhou,Meirong Bai,Jiarui Wu
出处
期刊:Computers in Biology and Medicine [Elsevier]
卷期号:152: 106460-106460 被引量:15
标识
DOI:10.1016/j.compbiomed.2022.106460
摘要

T cells are present in all stages of tumor formation and play an important role in the tumor microenvironment. We aimed to explore the expression profile of T cell marker genes, constructed a prognostic risk model based on these genes in Lung adenocarcinoma (LUAD), and investigated the link between this risk model and the immunotherapy response. We obtained the single-cell sequencing data of LUAD from the literature, and screened out 6 tissue biopsy samples, including 32,108 cells from patients with non-small cell lung cancer, to identify T cell marker genes in LUAD. Combined with TCGA database, a prognostic risk model based on T-cell marker gene was constructed, and the data from GEO database was used for verification. We also investigated the association between this risk model and immunotherapy response. Based on scRNA-seq data 1839 T-cell marker genes were identified, after which a risk model consisting of 9 gene signatures for prognosis was constructed in combination with the TCGA dataset. This risk model divided patients into high-risk and low-risk groups based on overall survival. The multivariate analysis demonstrated that the risk model was an independent prognostic factor. Analysis of immune profiles showed that high-risk groups presented discriminative immune-cell infiltrations and immune-suppressive states. Risk scores of the model were closely correlated with Linoleic acid metabolism, intestinal immune network for IgA production and drug metabolism cytochrome P450. Our study proposed a novel prognostic risk model based on T cell marker genes for LUAD patients. The survival of LUAD patients as well as treatment outcomes may be accurately predicted by the prognostic risk model, and make the high-risk population present different immune cell infiltration and immunosuppression state.
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