Department of Pharmacy, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Erheng Road of Yuan Village, Guangzhou, 510655, China.
Network Information Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Erheng Road of Yuan Village, Guangzhou, 510655, China.
Med Oncol. 2020 Oct 19;37(11):104. doi: 10.1007/s12032-020-01425-2.
Most colorectal cancer (CRC) patients are diagnosed with advanced stages and low prognosis. We aimed to identify potential diagnostic and prognostic biomarkers, as well as active small molecules of CRC. Microarray data (GSE9348, GSE35279, and GSE106582) were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified by the GEO2R platform. Common DEGs were selected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Cytoscape software was used to construct protein-protein interaction networks and identify hub genes. Hub genes were evaluated by Kaplan-Meier survival analysis in the GEPIA database and validated in two independent microarray data (GSE74602 and GSE83889). Common DEGs were used to select active small molecules by the connectivity map database. A total of 166 DEGs were identified as common DEGs. GO analysis demonstrated that common DEGs were significantly enriched in the apoptotic process, cell proliferation, and cell adhesion. KEGG analysis indicated that the most enriched pathways were the PI3K-Akt signaling pathway and extracellular matrix-receptor interaction. COL1A2, THBS2, TIMP1, and CXCL8 significantly upregulated in colorectal tumor. High expressions of COL1A2, THBS2, and TIMP1 were associated with poor survival, while high expressions of CXCL8 were associated with better survival. We selected 11 small molecules for CRC therapy. In conclusion, we found key dysregulated genes associated with CRC and potential small molecules to reverse them. COL1A2, THBS2, TIMP1, and CXCL8 may act as diagnostic and prognostic biomarkers of CRC.
大多数结直肠癌（CRC）患者被诊断为晚期且预后不良。我们旨在鉴定潜在的诊断和预后生物标志物以及 CRC 的活性小分子。从基因表达综合数据库中获取微阵列数据（GSE9348、GSE35279 和 GSE106582）。通过 GEO2R 平台鉴定差异表达基因（DEGs）。选择常见的 DEGs 进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。Cytoscape 软件用于构建蛋白质-蛋白质相互作用网络并鉴定枢纽基因。通过 GEPIA 数据库的 Kaplan-Meier 生存分析评估枢纽基因，并在两个独立的微阵列数据（GSE74602 和 GSE83889）中进行验证。通过连接图谱数据库，使用常见的 DEGs 选择活性小分子。共鉴定出 166 个 DEGs 作为常见 DEGs。GO 分析表明，常见的 DEGs 在细胞凋亡、细胞增殖和细胞黏附过程中显著富集。KEGG 分析表明，最丰富的途径是 PI3K-Akt 信号通路和细胞外基质-受体相互作用。COL1A2、THBS2、TIMP1 和 CXCL8 在结直肠肿瘤中显著上调。COL1A2、THBS2 和 TIMP1 的高表达与预后不良相关，而 CXCL8 的高表达与预后较好相关。我们选择了 11 种用于 CRC 治疗的小分子。总之，我们发现了与 CRC 相关的关键失调基因和潜在的小分子来逆转它们。COL1A2、THBS2、TIMP1 和 CXCL8 可能作为 CRC 的诊断和预后生物标志物。
