Investigation of Common Pathways and Putative Biomarker Candidates of Colorectal Cancer and Insomnia by Using Integrative In-Silico Approaches.

ABSTRACT

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortalities across the globe. Accumulating evidence shows that individuals having sleep disorders such as insomnia are at high risk of developing CRC, yet the association of sleep disorders with CRC risk is still unclear. Here, we investigated the potential molecular connections between CRC and insomnia using integrative in silico approaches. Objective: This study aims to explore the potential molecular connections between CRC and insomnia utilizing integrative in-silico methodologies. Methods and Methods: Gene expression microarray datasets for CRC and insomnia samples were retrieved from the NCBI-GEO database and analyzed using R. Functional enrichment analysis of common differentially expressed genes (DEGs) was performed by the g Profiler tool. Cytoscape software was used to construct a protein-protein interaction network and hub gene identification. Expression profiles of hub genes in TCGA datasets were also determined, and predicted miRNAs targeting hub genes were analyzed by miRNA target prediction tools. Results: Our results revealed a total of 113 shared DEGs between the CRC and insomnia datasets. Six genes (HSP8A, GAPDH, HSP90AA1, EEF1G, RPS6, and RPLP0), which were also differently expressed in TCGA datasets, were prioritized as hub genes and were found to be enriched in pathways related to protein synthesis. hsa-miR-324-3p, hsa-miR-769-3p, and hsa-miR-16-5p were identified as promising miRNA biomarkers for two diseases. Conclusions: Our in-silico analysis provides promising evidence of the molecular link between CRC and insomnia and highlights multiple potential molecular biomarkers and pathways. Validation of the results by wet lab work can be utilized for novel translational and precision medicine applications to alleviate the public health burden of CRC.