Han Chao, Jin Lei, Ma Xuemei, Hao Qin, Lin Huajun, Zhang Zhongtao
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
Open Med (Wars). 2020 May 30;15(1):403-412. doi: 10.1515/med-2020-0405. eCollection 2020.
This study identified key genes in gastric cancer (GC) based on the mRNA microarray GSE19826 from the Gene Expression Omnibus (GEO) database and preliminarily explored the relationships among the key genes.
Differentially expressed genes (DEGs) were obtained using the GEO2R tool. The functions and pathway enrichment of the DEGs were analyzed using the Enrichr database. Protein-protein interactions (PPIs) were established by STRING. A lentiviral vector was constructed to silence RUNX2 expression in MGC-803 cells. The expression levels of RUNX2 and FN1 were measured. The influences of RUNX2 and FN1 on overall survival (OS) were determined using the Kaplan-Meier plotter online tool.
In total, 69 upregulated and 65 downregulated genes were identified. Based on the PPI network of the DEGs, 20 genes were considered hub genes. RUNX2 silencing significantly downregulated the FN1 expression in MGC-803 cells. High expression of RUNX2 and low expression of FN1 were associated with long survival time in diffuse, poorly differentiated, and lymph node-positive GC.
High RUNX2 and FN1 expression were associated with poor OS in patients with GC. RUNX2 can negatively regulate the secretion of FN1, and both genes may serve as promising targets for GC treatment.
本研究基于基因表达综合数据库(GEO)中的mRNA微阵列GSE19826鉴定胃癌(GC)中的关键基因,并初步探讨关键基因之间的关系。
使用GEO2R工具获得差异表达基因(DEG)。使用Enrichr数据库分析DEG的功能和通路富集情况。通过STRING建立蛋白质-蛋白质相互作用(PPI)。构建慢病毒载体以沉默MGC-803细胞中RUNX2的表达。检测RUNX2和FN1的表达水平。使用Kaplan-Meier Plotter在线工具确定RUNX2和FN1对总生存期(OS)的影响。
共鉴定出69个上调基因和65个下调基因。基于DEG的PPI网络,20个基因被视为枢纽基因。RUNX2沉默显著下调MGC-803细胞中FN1的表达。RUNX2高表达和FN1低表达与弥漫性、低分化和淋巴结阳性GC患者的长生存期相关。
RUNX2和FN1高表达与GC患者的不良OS相关。RUNX2可负调控FN1的分泌,这两个基因可能是GC治疗的有前景的靶点。