Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210000, China.
Department of Cardiothoracic Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223300, China.
World J Surg Oncol. 2022 Mar 30;20(1):99. doi: 10.1186/s12957-022-02543-z.
Lung adenocarcinoma (LUAD) is one of the major subtypes of lung cancer that is associated with poor prognosis. The aim of this study was to identify useful biomarkers to enhance the treatment and diagnosis of LUAD.
GEO2R was used to identify common up-regulated differentially expressed genes (DEGs) in the GSE32863, GSE40791, and GSE75037 datasets. The DEGs were submitted to Metascape for gene ontology and pathway enrichment analysis as well as construction of the protein-protein interaction (PPI) network, while the molecular complex detection (MCODE) plug-in was employed to filter important subnetworks. The expression levels of the hub genes and their prognostic values were evaluated using the UALCAN, GEPIA2, and Kaplan-Meier plotter databases. The timer algorithm was utilized to determine the correlation between immune cell infiltration and the expression levels of hub genes in LUAD tissues. In addition, the hub gene mutation landscape and the correlation analysis with tumor mutational burden (TMB) score were evaluated using maftools package and ggstatsplot package in R software, respectively.
We identified 156 common up-regulated DEGs, with gene ontology and pathway enrichment analysis indicating that they were mostly enriched in mitotic cell cycle process and cell cycle pathway. DEGs in the subnetwork with the largest number of genes were AURKB, CCNB2, CDC20, CDCA5, CDCA8, CENPF, and KNTC1. The seven hub genes were highly expressed in LUAD tissues and were associated with poor prognosis. These hub genes were negatively correlated with most immune cells. The somatic mutation landscape showed that AURKB, CDC20, CENPF, and KNTC1 had mutations and were positively correlated with TMB scores.
Our findings demonstrate that increased expression of seven hub genes is associated with poor prognosis for LUAD patients. Additionally, the TMB score indicates that the high expression of hub gene increases immune cell infiltration in patients with lung adenocarcinoma which may significantly improve response to immunotherapy.
肺腺癌（LUAD）是肺癌的主要亚型之一，与预后不良有关。本研究旨在鉴定有用的生物标志物，以增强 LUAD 的治疗和诊断。
使用 GEO2R 鉴定 GSE32863、GSE40791 和 GSE75037 数据集之间常见的上调差异表达基因（DEG）。将 DEG 提交给 Metascape 进行基因本体论和途径富集分析以及构建蛋白质-蛋白质相互作用（PPI）网络，同时使用分子复合物检测（MCODE）插件筛选重要的子网络。使用 UALCAN、GEPIA2 和 Kaplan-Meier plotter 数据库评估关键基因的表达水平及其预后价值。使用 timer 算法确定 LUAD 组织中免疫细胞浸润与关键基因表达水平之间的相关性。此外，使用 maftools 包和 ggstatsplot 包在 R 软件中分别评估关键基因突变景观及其与肿瘤突变负担（TMB）评分的相关性分析。
我们鉴定出 156 个常见的上调 DEG，基因本体论和途径富集分析表明，它们主要富集在有丝分裂细胞周期过程和细胞周期途径中。子网络中基因数量最多的 DEG 是 AURKB、CCNB2、CDC20、CDCA5、CDCA8、CENPF 和 KNTC1。七个关键基因在 LUAD 组织中高表达，并与预后不良相关。这些关键基因与大多数免疫细胞呈负相关。体细胞突变景观表明，AURKB、CDC20、CENPF 和 KNTC1 发生突变，并且与 TMB 评分呈正相关。
我们的研究结果表明，七个关键基因的高表达与 LUAD 患者的预后不良相关。此外，TMB 评分表明，关键基因的高表达增加了肺腺癌患者的免疫细胞浸润，这可能显著提高免疫治疗的反应。
