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 ~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.
Highlights
Colorectal cancer (CRC) is one of the most common types of tumors and is the third leading cause of death among cancer patients worldwide (Siegel et al, 2020)
We aimed to confirm a detailed molecular mechanism to identify the prognostic genes and potential drug-repurposing for CRC, which might provide preliminary bioinformatic evidence to better understand the complex mechanism of CRC progression and which might help improve the outcome of CRC
We identified the interactions among the hub genes and core genes involved in key pathways using the Protein-protein interaction (PPI) and shortest path analysis
Summary
Colorectal cancer (CRC) is one of the most common types of tumors and is the third leading cause of death among cancer patients worldwide (Siegel et al, 2020). Since the prognosis of CRC mainly depends on the clinicopathological features or the tumor stage (Messersmith, 2019), many patients are still diagnosed at advanced stages, and the 5-year survival rate is only ∼30% (Siegel et al, 2020). Recent studies have documented some prognostic related biomarkers in CRC. Upregulated CIP2A could contribute to tumor cell survival and a poor prognosis in CRC (Liu et al, 2018). Overexpression of HOXB13 in CRC could inhibit the tumor growth and be related to the poor outcome (Xie et al, 2019).
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