Utilizing an In-silico Approach to Pinpoint Potential Biomarkers for Enhanced Early Detection of Colorectal Cancer

Abstract

Objectives: Colorectal cancer (CRC) is a prevalent disease characterized by significant dysregulation of gene expression. Non-invasive tests that utilize microRNAs (miRNAs) have shown promise for early CRC detection. This study aims to determine the association between miRNAs and key genes in CRC.

Methods: Two datasets (GSE106817 and GSE23878) were extracted from the NCBI Gene Expression Omnibus database. Penalized logistic regression (PLR) and artificial neural networks (ANN) were used to identify relevant miRNAs and evaluate the classification accuracy of the selected miRNAs. The findings were validated through bipartite miRNA-mRNA interactions.

Results: Our analysis identified 3 miRNAs: miR-1228, miR-6765-5p, and miR-6787-5p, achieving a total accuracy of over 90%. Based on the results of the mRNA-miRNA interaction network, CDK1 and MAD2L1 were identified as target genes of miR-6787-5p.

Conclusions: Our results suggest that the identified miRNAs and target genes could serve as non-invasive biomarkers for diagnosing colorectal cancer, pending laboratory confirmation.

Keywords: Colorectal neoplasms; artificial neural networks; least absolute shrinkage and selection operator; microRNA; smoothly clipped absolute deviation; the minimax concave penalty.

Figure 1.

Flow chart of bioinformatics analysis.

Figure 2.

The overlap between the top 10 predicted target genes, ranked by MNC, EPC, and DEGREE illustrated in a Venn diagram. The number 7 in the image’s center describes the 3 groups’ commonalities.

Figure 3.

Gene Ontology (GO) and KEGG pathway enrichment analyses were performed for the module genes. The top 10 GO terms in Biological Process (BP), Molecular Function (MF), and Cellular Component (CC), along with significant KEGG pathways, are presented.

Figure 4.

Bipartite mRNA-miRNA subnetwork for CRC. Blue diamonds consist of hub genes between CRC and normal tissues. Green diamonds consist of 2 hub genes targeting miR-6787. Cytoscape v.3.8.2 was used to visualize the network.

Figure 5.

Validation of hub genes in colorectal cancer using TCGA-COAD. Two hub genes including CDK1, and MAD2L1 were significantly upregulated in CRC tissues compared to normal tissues in TCGA- COAD data.