广西医学

目的利用生物信息学筛选胃癌相关关键基因，并探讨关键基因的临床价值。方法（1）从GEO数据库中获取与人类胃癌相关的3个基因芯片数据集，利用在线分析工具GEO2R获取差异表达基因(DEGs)。针对3个数据集共有的DEGs，利用DAVID数据库进行富集分析，利用STRING数据库构建蛋白-蛋白相互作用（PPI）网络后通过Cytoscape 3.9.1软件筛选关键基因。（2）收集20例胃癌患者的癌组织及癌旁正常组织，利用实时荧光定量PCR法检测关键基因的表达水平。利用GEPIA2数据库分析关键基因在胃癌组织与癌旁正常组织的表达差异，以及在不同病理分期胃癌患者中的表达差异。利用Kaplan-Meier Plotter数据库分析不同关键基因表达水平的胃癌患者的生存情况。结果（1）共获得461个共同DEGs，包括190个上调DEGs、271个下调DEGs。DEGs主要参与细胞外基质形成、胶原纤维、细胞-基质黏附等生物过程，主要富集在细胞外基质-受体相互作用、蛋白质消化吸收、黏着斑等信号通路。共筛选出5个关键基因，即COL4A1、COL4A2、LUM、COL6A3和SPARC。（2）实时荧光定量PCR及GEPIA2数据库验证结果显示，5个关键基因在胃癌组织中的表达水平均高于癌旁正常组织，且LUM、COL6A3、SPARC的表达与胃癌患者的病理分期有关（P＜0.05）；Kaplan-Meier Plotter数据库分析结果显示，COL4A1、COL4A2、COL6A3、SPARC的高表达及LUM的低表达与胃癌患者预后不良相关（P＜0.05）。结论COL4A1、COL4A2、LUM、COL6A3和SPARC基因可能在胃癌的发生与发展中发挥关键作用，有望成为胃癌的潜在分子标志物。

ObjectiveTo screen gastric the cancer-related key genes by using bioinformatics, and to investigate the clinical value of the key genes. Methods(1) A total of 3 datasets of gene chips related to human gastric cancer were obtained from the GEO database, and the online analyzer GEO2R was used to acquire differentially expressed genes (DEGs). For DEGs common to all 3 datasets, the DAVID database was employed to perform enrichment analysis, and after the establishment of protein-protein interaction (PPI) network by the STRING database, the key genes were screened through the Cytoscape 3.9.1 software. (2) Cancerous tissues and paracancerous normal tissues of 20 patients with gastric cancer were collected, and expressions of the key genes were detected by using the real-time fluorescent quantitative PCR. The GEPIA2 database was employed to analyze expression differences of the key genes between gastric cancerous tissues and paracancerous normal tissues, and between patients with gastric cancer in different pathological stages. The Kaplan-Meier Plotter database was used to analyze survival status of patients with gastric cancer in different expressions of the key genes. Results(1) A total of 461 common DEGs were obtained, including 190 up-regulated DEGs and 271 down-regulated DEGs, and these DEGs were mainly involved in biological processes with respect to extracellular matrix formation, collagen fiber, cell-matrix adhesion, etc., mainly enriched in signaling pathways in terms of extracellular matrix-receptor interaction, protein digestion and absorption, and focal adhesion, etc. Five key genes were screened in total, containing COL4A1, COL4A2, LUM, COL6A3, and SPARC. (2) The validation results of real-time fluorescent quantitative PCR and GEPIA2 database revealed that expressions of the five key genes in gastric cancerous tissues were higher than those in paracancerous normal tissues, and LUM, COL6A3, and SPARC expressions were related to pathological stages in patients with gastric cancer (P＜0.05). The analysis results of Kaplan-Meier Plotter database presented that high expressions of COL4A1, COL4A2, COL6A3, SPARC, and low expression of LUM correlated with adverse prognosis of patients with gastric cancer (P＜0.05). ConclusionCOL4A1, COL4A2, LUM, COL6A3, and SPARC genes may play a key role in the occurrence and development of gastric cancer, which may be regarded as potential molecular markers for gastric cancer.