Long Xuan, Deng Zhigang, Li Guoqiang, Wang Ziwei
1Department of Gastroenterological Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, 1# Youyi Road, Chongqing, 400016 People's Republic of China.
2Department of General Surgery, Mianyang Central Hospital, Mianyang, 621000 Sichuan People's Republic of China.
Cancer Cell Int. 2018 Sep 17;18:139. doi: 10.1186/s12935-018-0640-x. eCollection 2018.
The purpose of this study was to screen the critical genes for future diagnosis and treatment of colon cancer by bioinformatics method.
In this study, we used bioinformatics approaches to identify gene alteration that contribute to colon cancer progression via analysis of TCGA RNA sequencing data and other publicly GEO microarray data. The Random forest survival model was used to screen gene sets related to the prognosis in DEGs. Gene ontology and KEGG pathway enrichment analysis were performed to determine the potential function of DEGs.
We identified versican (VCAN), a member of the aggrecan/versican proteoglycan family, as a key regulator in human colon cancer development and progression involved in cell adhesion, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance. Interestingly, we found that VCAN is highly over-expressed in colon cancer and increased expression of VCAN was associated with the progression of colon cancer. High VCAN levels also predict shorter overall survival of colon cancer patients. Furthermore, in vitro assays of silencing VCAN inhibit HCT116 cell proliferation and invasion.
These data demonstrated VCAN were associated with tumorigenesis and may be as biomarker for identification of the pathological grade of colon cancer.
本研究旨在通过生物信息学方法筛选用于未来结肠癌诊断和治疗的关键基因。
在本研究中,我们运用生物信息学方法,通过分析TCGA RNA测序数据及其他公开的GEO微阵列数据,来识别促成结肠癌进展的基因改变。随机森林生存模型用于筛选与差异表达基因(DEGs)预后相关的基因集。进行基因本体论和KEGG通路富集分析以确定DEGs的潜在功能。
我们鉴定出多功能蛋白聚糖(VCAN),它是聚集蛋白聚糖/多功能蛋白聚糖蛋白聚糖家族的成员,是人类结肠癌发生和进展中的关键调节因子,参与细胞黏附、增殖、迁移和血管生成,并在组织形态发生和维持中起核心作用。有趣的是,我们发现VCAN在结肠癌中高度过表达,且VCAN表达增加与结肠癌进展相关。高VCAN水平还预示着结肠癌患者的总生存期较短。此外,沉默VCAN的体外实验抑制了HCT116细胞的增殖和侵袭。
这些数据表明VCAN与肿瘤发生相关,可能作为鉴定结肠癌病理分级的生物标志物。