Department of General Surgery, The First Affiliated Hospital of JinZhou Medical University, No.2, Section 5, People Street, JinZhou, LiaoNing, 121000, People's Republic of China.
Int J Surg. 2018 Nov;59:80-89. doi: 10.1016/j.ijsu.2018.09.020. Epub 2018 Oct 5.
Colorectal cancer (CRC) is one of the most common cancers worldwide. The aim of this study is to identify candidate genes by bioinformatics and investigate its clinical pathological characters and prognostic significance.
First, we identify differentially expressed genes (DEGs) in CRC by analyzing gene expression datasets from Gene Expression Omnibus (GEO). Then we performed a bioinformatics analysis by using Oncomine, STRING and Oncolnc databases. Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. Then, the protein expression level of PPP2CA was detected by immunohistochemistry in 196 pairs of primary colorectal cancer and corresponding non-tumor tissues.
Total 81 differential expressed genes were identified in the overlap of datasets. PPI network show the hub genes were CCND1, PPP2CA and YAP1. We investigated Oncomine databases and found that PPP2CA mRNA expression was lower in CRC tissues compared with normal tissues. Bioinformatics analysis indicated that PPP2CA expression was associated with epithelial-mesenchymal transition signaling pathway. Low expression of PPP2CA was associated with T stage, N stage, and M stage. Low expression of PPP2CA was associated with worse overall survival for CRC, and retained significance as an independent prognostic factor for CRC.
PPP2CA may act as an oncogene in the progression of colorectal cancer. Moreover, PPP2CA has potential to be used as prognostic markers or therapeutic targets in CRC.
结直肠癌(CRC)是全球最常见的癌症之一。本研究旨在通过生物信息学方法鉴定候选基因,并探讨其临床病理特征和预后意义。
首先,我们通过分析基因表达数据集(来自 GEO)来鉴定 CRC 中的差异表达基因(DEGs)。然后,我们使用 Oncomine、STRING 和 OncoLnc 数据库进行了生物信息学分析。使用 TCGA 数据集进行基因集富集分析(GSEA)。然后,通过免疫组织化学法检测 196 对原发性结直肠癌及其相应非肿瘤组织中 PPP2CA 的蛋白表达水平。
在数据集的重叠部分共鉴定出 81 个差异表达基因。PPI 网络显示,CCND1、PPP2CA 和 YAP1 是关键基因。我们研究了 Oncomine 数据库,发现 PPP2CA 在 CRC 组织中的 mRNA 表达低于正常组织。生物信息学分析表明,PPP2CA 的表达与上皮-间充质转化信号通路有关。PPP2CA 表达水平低与 T 分期、N 分期和 M 分期有关。PPP2CA 表达水平低与 CRC 的总生存期较差相关,并且作为 CRC 的独立预后因素仍然具有显著意义。
PPP2CA 可能在结直肠癌的进展中起致癌基因的作用。此外,PPP2CA 有可能成为 CRC 的预后标志物或治疗靶点。