Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China.
Department of Radiation Oncology, Shandong Provincial Cancer Hospital, Jinan 250117, Shandong, China.
Aging (Albany NY). 2020 Mar 25;12(6):4757-4777. doi: 10.18632/aging.102871.
Non-small cell lung cancer (NSCLC), which consists mainly of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), are the leading cause of cancer deaths worldwide. In this study, we performed a comprehensive analysis of the tumor microenvironmental and genetic factors to identify prognostic biomarkers for NSCLC. We evaluated the immune and stromal scores of patients with LUAD and LUSC using data from The Cancer Genome Atlas database with the ESTIMATE algorithm. Based on these scores, the differentially expressed genes were obtained and immune-related prognostic genes were identified. Functional analysis and protein-protein interaction network further revealed the immune-related biological processes in which these genes participated. Additionally, 22 subsets of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment were analyzed with the CIBERSORT algorithm. Finally, we validated these valuable genes using an independent cohort from the Gene Expression Omnibus database. The associations of the immune and stromal scores with patients' clinical characteristics and prognosis were positive in LUAD but negative in LUSC and the correlations of TIICs with clinical characteristics were clarified. Several differentially expressed genes were identified to be potential immune-related prognostic genes. This study comprehensively analyzed the tumor microenvironment and presented immune-related prognostic biomarkers for NSCLC.
非小细胞肺癌(NSCLC)主要包括肺腺癌(LUAD)和肺鳞状细胞癌(LUSC),是全球癌症死亡的主要原因。在这项研究中,我们对肿瘤微环境和遗传因素进行了全面分析,以确定 NSCLC 的预后生物标志物。我们使用 ESTIMATE 算法从癌症基因组图谱(TCGA)数据库评估了 LUAD 和 LUSC 患者的免疫和基质评分。基于这些评分,获得了差异表达基因,并鉴定了与免疫相关的预后基因。功能分析和蛋白质-蛋白质相互作用网络进一步揭示了这些基因参与的免疫相关生物学过程。此外,使用 CIBERSORT 算法分析了肿瘤微环境中 22 个肿瘤浸润免疫细胞(TIC)亚群。最后,我们使用来自基因表达综合数据库(GEO)的独立队列验证了这些有价值的基因。在 LUAD 中,免疫和基质评分与患者的临床特征和预后呈正相关,但在 LUSC 中呈负相关,并且阐明了 TICs 与临床特征的相关性。确定了几个差异表达基因作为潜在的免疫相关预后基因。本研究全面分析了肿瘤微环境,并为 NSCLC 提供了与免疫相关的预后生物标志物。