Exploring Core Genes by Comparative Transcriptomics Analysis for Early Diagnosis, Prognosis, and Therapies of Colorectal Cancer

SIMPLE SUMMARY: Colorectal cancer (CRC) is a complex disease that has a high mortality rate. This study explored CRC-related core genes (CGs) from multiple microarray gene-expression profiles in the NCBI-GEO database by combining some statistics and bioinformatics techniques. It also disclosed their molecular functions, biological processes, cellular components, signaling pathways, and transcriptional and post-transcriptional regulatory factors by using different online bioinformatics tools and databases. The prognostic power of CGs was investigated from the independent TCGA database by using survival probability curves and box plots of CGs-expressions in different stages (control, Stage 1, Stage 2, Stage 3, and Stage 4) of CRC. Finally, a few CGs-guided drug molecules were suggested for the treatment of CRC by molecular docking and dynamic simulation studies. Therefore, the findings of this study would be useful resources for early diagnosis, prognosis, and therapies of CRC. ABSTRACT: Colorectal cancer (CRC) is one of the most common cancers with a high mortality rate. Early diagnosis and therapies for CRC may reduce the mortality rate. However, so far, no researchers have yet investigated core genes (CGs) rigorously for early diagnosis, prognosis, and therapies of CRC. Therefore, an attempt was made in this study to explore CRC-related CGs for early diagnosis, prognosis, and therapies. At first, we identified 252 common differentially expressed genes (cDEGs) between CRC and control samples based on three gene-expression datasets. Then, we identified ten cDEGs (AURKA, TOP2A, CDK1, PTTG1, CDKN3, CDC20, MAD2L1, CKS2, MELK, and TPX2) as the CGs, highlighting their mechanisms in CRC progression. The enrichment analysis of CGs with GO terms and KEGG pathways revealed some crucial biological processes, molecular functions, and signaling pathways that are associated with CRC progression. The survival probability curves and box-plot analyses with the expressions of CGs in different stages of CRC indicated their strong prognostic performance from the earlier stage of the disease. Then, we detected CGs-guided seven candidate drugs (Manzamine A, Cardidigin, Staurosporine, Sitosterol, Benzo[a]pyrene, Nocardiopsis sp., and Riccardin D) by molecular docking. Finally, the binding stability of four top-ranked complexes (TPX2 vs. Manzamine A, CDC20 vs. Cardidigin, MELK vs. Staurosporine, and CDK1 vs. Riccardin D) was investigated by using 100 ns molecular dynamics simulation studies, and their stable performance was observed. Therefore, the output of this study may play a vital role in developing a proper treatment plan at the earlier stages of CRC.