Chen Yingji, Jin Longyu, Jiang Zhibin, Liu Suo, Feng Wei
Department of Cardiothoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, China.
Front Oncol. 2021 Apr 16;11:644426. doi: 10.3389/fonc.2021.644426. eCollection 2021.
Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. At present, most patients with LUAD are diagnosed at an advanced stage, and the prognosis of advanced LUAD is poor. Hence, we aimed to identify novel biomarkers for the diagnosis and treatment of early stage LUAD and to explore their predictive value.
The microarray datasets GSE63459, GSE27262, and GSE33532 were searched, and the differentially expressed genes (DEGs) were obtained using GEO2R. The DEGs were subjected to gene ontology (GO) and pathway enrichment analyses using METASCAPE. A protein-protein interaction (PPI) network was plotted with STRING and visualized by Cytoscape. Module analysis of the PPI network was performed using MCODE. Overall survival (OS) analysis and analysis of the mRNA expression levels of genes identified by MCODE were performed with UALCAN. Western blot analysis of hub genes in LUAD patients, MTS assays, and clonogenic assays were performed to test the effects of the hub genes on cell proliferation .
A total of 341 DEGs were obtained, which were mainly enriched in terms related to blood vessel development, growth factor binding, and extracellular matrix organization. A PPI network consisting of 300 nodes and 1140 edges was constructed, and a significant module including 15 genes was identified. Elevated expression of ASPM, CCNB2, CDCA5, PRC1, KIAA0101, and UBE2T was associated with poor OS in LUAD patients. In the protein level, the hub gene was overexpressed in LUAD patients. experiments showed that knockdown of the hub genes in the LUAD cell lines could promote cell proliferation.
DEGs are potential biomarkers for early stage lung adenocarcinoma and could have utility for the diagnosis and predicting treatment efficacy.
肺腺癌（LUAD）是肺癌最常见的病理类型。目前，大多数LUAD患者在晚期被诊断出来，晚期LUAD的预后较差。因此，我们旨在鉴定用于早期LUAD诊断和治疗的新型生物标志物，并探讨其预测价值。
搜索微阵列数据集GSE63459、GSE27262和GSE33532，并使用GEO2R获得差异表达基因（DEG）。使用METASCAPE对DEG进行基因本体（GO）和通路富集分析。用STRING绘制蛋白质-蛋白质相互作用（PPI）网络，并通过Cytoscape进行可视化。使用MCODE对PPI网络进行模块分析。用UALCAN进行总生存期（OS）分析以及对MCODE鉴定的基因的mRNA表达水平进行分析。对LUAD患者的枢纽基因进行蛋白质印迹分析、MTS试验和克隆形成试验，以测试枢纽基因对细胞增殖的影响。
共获得341个DEG，主要富集于与血管发育、生长因子结合和细胞外基质组织相关的术语。构建了一个由300个节点和1140条边组成的PPI网络，并鉴定出一个包含15个基因的显著模块。ASPM、CCNB2、CDCA5、PRC1、KIAA0101和UBE2T的表达升高与LUAD患者的不良OS相关。在蛋白质水平上，枢纽基因在LUAD患者中过表达。实验表明，在LUAD细胞系中敲低枢纽基因可促进细胞增殖。
DEG是早期肺腺癌的潜在生物标志物，可用于诊断和预测治疗效果。
