Zhang Lemeng, Chen Jianhua, Cheng Tianli, Yang Hua, Li Haitao, Pan Changqie
Thoracic Medicine Department 1, Hunan Cancer Hospital, Changsha, Hunan Province, P.R. China, 410013.
J Cancer. 2020 Jun 16;11(17):4965-4979. doi: 10.7150/jca.42531. eCollection 2020.
This study aimed to investigate the key genes and immune microenvironment involved in different TNM stages of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The gene expression and clinical characteristics data were downloaded from the genomic data commons (GDC) database. After initial data processing, the characteristics of the immune microenvironment were analyzed. The differentially expressed genes (DEGs) in tumor vs. normal, and in early vs. advanced stages were screened, followed by Spearman correlation test for tumor infiltrating immune cells (TIICs) to identify immune-related genes. Finally, functional enrichment, protein-protein interaction, and survival analyses were performed. In LUAD, early stage was with higher immune scores, greater number of memory B cells and M0 macrophages compared to advanced stage. M0 and M2 macrophages, and resting memory CD4+ T cells accounted for a large proportion of TIICs in LUAD. The abundance of M0 macrophage infiltration was significantly correlated with the TNM stage and survival. In LUSC, early stage was with higher cytolytic activity and neoantigen burden compared to advanced stage. M0 and M2 macrophages, and plasma cells accounted for a large proportion of TIICs in LUSC. The abundance of resting and activated mast cells was significantly correlated with TNM stage, while resting dendritic cells, eosinophils, activated memory CD4 T cells, and mast cells were significantly correlated with prognosis. Tumor mutation burden analysis revealed that the median of variants per sample decreased from stage I to IV in LUAD, while it increased in LUSC. Further, 83 and 9 immune-related DEGs were identified in LUAD and LUSC, respectively, of which 23 genes in LUAD and 2 genes in LUSC correlated with survival. In conclusion, we identified the key genes, and characterized the tumor immune microenvironment in LUAD and LUSC which may provide therapeutic targets for the treatment of NSCLC.
本研究旨在探究肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）不同TNM分期中涉及的关键基因和免疫微环境。基因表达和临床特征数据从基因组数据共享库（GDC）数据库下载。经过初步数据处理后，对免疫微环境的特征进行了分析。筛选肿瘤与正常组织以及早期与晚期之间的差异表达基因（DEG），随后对肿瘤浸润免疫细胞（TIIC）进行Spearman相关性检验以鉴定免疫相关基因。最后进行了功能富集、蛋白质 - 蛋白质相互作用和生存分析。在LUAD中，与晚期相比，早期具有更高的免疫评分、更多的记忆B细胞和M0巨噬细胞。M0和M2巨噬细胞以及静息记忆CD4 + T细胞在LUAD的TIIC中占很大比例。M0巨噬细胞浸润的丰度与TNM分期和生存显著相关。在LUSC中，与晚期相比，早期具有更高的细胞溶解活性和新抗原负荷。M0和M2巨噬细胞以及浆细胞在LUSC的TIIC中占很大比例。静息和活化肥大细胞的丰度与TNM分期显著相关，而静息树突状细胞、嗜酸性粒细胞、活化记忆CD4 T细胞和肥大细胞与预后显著相关。肿瘤突变负荷分析显示，LUAD中每个样本的变异中位数从I期到IV期下降，而在LUSC中则增加。此外，分别在LUAD和LUSC中鉴定出83个和9个免疫相关DEG，其中LUAD中的23个基因和LUSC中的2个基因与生存相关。总之，我们鉴定了关键基因，并对LUAD和LUSC中的肿瘤免疫微环境进行了特征描述，这可能为非小细胞肺癌的治疗提供治疗靶点。
