Identification Of A Five-Gene Prognostic Model And Its Potential Drug Repurposing In Colorectal Cancer Based On Tcga, Gtex And Geo Databases

FRONTIERS IN GENETICS(2021)

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Abstract
Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Unfortunately, many CRC patients are still being diagnosed at an advanced stage of the cancer, and the 5-year survival rate is only similar to 30%. Effective prognostic markers of CRC are therefore urgently needed. To address this issue, we performed a detailed bioinformatics analysis based on the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases to identify prognostic biomarkers for CRC, which in turn help in exploring potential drug-repurposing. We identified five hub genes (PGM2, PODXL, RHNO1, SCD, and SEPHS1), which had good performance in survival prediction and might be involved in CRC through three key pathways ("Cell cycle," "Purine metabolism," and "Spliceosome" KEGG pathways) identified by a KEGG pathway enrichment analysis. What is more, we performed a co-expression analysis between five hub genes and transcription factors to explore the upstream regulatory region. Furthermore, we screened the potential drug-repurposing for the five hub genes in CRC according to the Binding DB and ZINC15 databases. Taking together, we constructed a five-gene signature to predict overall survival of CRC and found the potential drug-repurposing, which may improve the outcome of CRC in the future.
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Key words
colorectal cancer, mechanisms, prognosis, drug-repurposing, WGCNA
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