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鉴定肺腺癌肿瘤微环境中的关键基因。

Identification of key genes in the tumor microenvironment of lung adenocarcinoma.

机构信息

Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, P. R. China.

Department of Interventional Vascular Surgery, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, P. R. China.

出版信息

Med Oncol. 2021 Jun 12;38(7):83. doi: 10.1007/s12032-021-01529-3.

Abstract

The tumor microenvironment plays an important role in tumor development and progression, but the role of immune and stromal cells in this environment has not been sufficiently studied. In this study, we aimed to identify key genes associated with the microenvironment of lung adenocarcinoma (LUAD). Raw data for stromal and immune cells in malignant tumors were downloaded from The Cancer Genome Atlas (TCGA). These expression data were used to identify the differentially expressed genes (DEGs) in tissue samples of LUAD with high and low immune scores. A protein-protein interaction (PPI) network based on genes with significant differential expression was constructed. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to functionally annotate putative hub genes. These genes were assessed via Kaplan Meier analysis to determine their correlation with overall survival. In total, we identified 216 DEGs which were correlated with immune and stromal scores, including 30 hub genes which were identified based on the PPI network. Further analysis suggested that the expression levels of 10 of these genes were significantly correlated with overall survival of LUAD patients. These key hub genes included CCR2, CCR5, CD53, CYBB, HCK, IRF8, LCP2, PLEK, PTPRC, and TLR7. Moreover, the expression level of CCR2 was found to have strong prognostic value for LUAD patients. Additionally, high expression of CYBB was also correlated with better survival of patients with LUAD. The results of this study open several new avenues to explore in the treatment of LUAD.

摘要

肿瘤微环境在肿瘤的发生和发展中起着重要作用,但免疫和基质细胞在这一环境中的作用尚未得到充分研究。在这项研究中,我们旨在确定与肺腺癌(LUAD)微环境相关的关键基因。从癌症基因组图谱(TCGA)下载了恶性肿瘤中基质和免疫细胞的原始数据。这些表达数据用于鉴定免疫评分高低的 LUAD 组织样本中的差异表达基因(DEGs)。基于具有显著差异表达的基因构建了蛋白质-蛋白质相互作用(PPI)网络。此外,还进行了基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析,以对假定的枢纽基因进行功能注释。通过 Kaplan-Meier 分析评估这些基因,以确定它们与总生存期的相关性。总共鉴定出 216 个与免疫和基质评分相关的 DEG,其中 30 个枢纽基因基于 PPI 网络确定。进一步分析表明,其中 10 个基因的表达水平与 LUAD 患者的总生存期显著相关。这些关键的枢纽基因包括 CCR2、CCR5、CD53、CYBB、HCK、IRF8、LCP2、PLEK、PTPRC 和 TLR7。此外,CCR2 的表达水平被发现对 LUAD 患者具有很强的预后价值。此外,CYBB 的高表达也与 LUAD 患者的生存改善相关。这项研究的结果为 LUAD 的治疗开辟了几条新的探索途径。

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