Identification of candidate biomarkers and therapeutic drugs of colorectal cancer by integrated bioinformatics analysis.
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.
['Zheng|Zhuoling|Z|', 'Xie|Jingwen|J|', 'Xiong|Lixiong|L|', 'Gao|Min|M|', 'Qin|Li|L|', 'Dai|Chunmei|C|', 'Liang|Zhikun|Z|', 'Wang|Yiting|Y|', 'Xue|Jing|J|', 'Wang|Qinbo|Q|', 'Wang|Wenhui|W|', 'Li|Xiaoyan|X|http://orcid.org/0000-0003-3145-0517']
D000970:Antineoplastic Agents D014408:Biomarkers, Tumor D015179:Colorectal Neoplasms D019295:Computational Biology D030541:Databases, Genetic D015972:Gene Expression Regulation, Neoplastic D063990:Gene Ontology D006801:Humans D011379:Prognosis D060066:Protein Interaction Maps D015203:Reproducibility of Results D015398:Signal Transduction D054852:Small Molecule Libraries D016019:Survival Analysis D059467:Transcriptome
Biomarker Colorectal cancer COL1A2 THBS2 TIMP1 CXCL8