Yang Zhou, Chen Yusheng, Wu Dejun, Min Zhijun, Quan Yingjun
Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, People's Republic of China.
Onco Targets Ther. 2019 May 22;12:3991-4000. doi: 10.2147/OTT.S207390. eCollection 2019.
This study aimed to find risk factors for colon cancer progression with bioinformatics methods, and validated by clinical patients. Differentially expressed genes (DEGs) between colon cancer tissues and normal colon tissues were extracted from The Cancer Genome Atlas (TCGA) database using R software, amounted to 8,051. DEGs between pathologic stage I+II and stage III+IV amounted to 373, and were compared with DEGs of cancer/normal analyzed above to get the intersection of both. Ninety-six intersected DEGs were identified and defined as progressive DEGs of colon cancer. Then these 96 progressive DEGs were studied by Gene ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis using the DAVID database and visualizing by R software. A protein-protein interaction (PPI) network and functional modules were established using the STRING database. Further, an overall survival (OS) curve was drawn via the GEPIA website based on the CGA database and six progressive DEGs were found to be involved with OS of colon cancer patients. The Linkedomics website was used for detailed analysis of specific subsets of TNM. Pregnancy specific glycoprotein (PSG), vitamin digestion, and absorption were confirmed to promote the progression of colon cancer. Furthermore, NTF4 was found to be associated with both OS and each subset of TNM; therefore, defined as a key risk factor for colon cancer progression. Further analysis of NTF4 expression using clinical data showed it acted as a key risk factor and diagnosis marker for colon cancer progression. NTF4 is a risk factor contributing to colon cancer progression and associated with overall survival.
本研究旨在运用生物信息学方法寻找结肠癌进展的危险因素，并通过临床患者进行验证。使用R软件从癌症基因组图谱（TCGA）数据库中提取结肠癌组织与正常结肠组织之间的差异表达基因（DEG），共8051个。病理I+II期与III+IV期之间的DEG有373个，并将其与上述癌症/正常组织的DEG进行比较以获得两者的交集。确定了96个相交的DEG，并将其定义为结肠癌的进展性DEG。然后使用DAVID数据库对这96个进展性DEG进行基因本体论和KEGG（京都基因与基因组百科全书）通路分析，并通过R软件进行可视化。使用STRING数据库建立蛋白质-蛋白质相互作用（PPI）网络和功能模块。此外，通过GEPIA网站基于CGA数据库绘制总生存（OS）曲线，发现6个进展性DEG与结肠癌患者的OS相关。使用Linkedomics网站对TNM的特定子集进行详细分析。证实妊娠特异性糖蛋白（PSG）、维生素消化和吸收促进结肠癌进展。此外，发现NTF4与OS以及TNM的每个子集均相关；因此，将其定义为结肠癌进展的关键危险因素。使用临床数据对NTF4表达进行进一步分析表明，它是结肠癌进展的关键危险因素和诊断标志物。NTF4是导致结肠癌进展并与总生存相关的危险因素。
