Computational network analysis of two popular skin cancers provides insights into the molecular mechanisms and reveals common therapeutic targets.

Abstract

Basal Cell Carcinoma (BCC) and Actinic Keratosis (AK) are prevalent skin conditions with significant health complications. The molecular mechanisms underlying these conditions and their potential shared pathways remain ambiguous despite their prevalence. Therefore, this study aims to elucidate the common molecular pathways and potential therapeutic targets for BCC and AK through comprehensive computational network analysis. Linkage analysis was performed to identify common liable genes between BCC and AK. Protein-protein interactions (PPIs), Topological properties, GO enrichment, pathway enrichment, and gene regulatory network analyses were also performed to reveal potential molecular mechanisms and pathways. Furthermore, we evaluated protein-drug interactions (PDIs) to identify potential therapeutic targets. Our analysis revealed 22 common genes between BCC and AK: TP53, EGFR, CDKN2A, MMP9, PTGS2, VDR, BCL2, MMP2, EZH2, TP63, FOXP3, MSH2, MMP14, FLG, MC1R, CDKN2B, TIMP3, TYR, SOX10, IRF4, KRT17, and NID1. PPI network analysis highlighted TP53 and EGFR as central hubs, validated using RNA-seq data. Co-expression and physical interaction analysis revealed a strong interplay between the common genes at the transcriptional and functional levels. GO analysis identified skin cancer-relevant terms: "skin development", "immune system development", and "response to radiation" as significantly enriched biological processes, while pathway enrichment analysis highlighted several cancer-related pathways enrichment. Gene regulatory network analysis revealed complex interactions between genes, miRNAs, and transcription factors, with TP53, BCL2, and EGFR playing central roles. PDI network analysis identified ibuprofen as a potential therapeutic agent targeting PTGS2 and BCL2, while other proteins VDR, MMP2, MMP9, and TYR showed interactions with multiple drugs. This computational analysis provides valuable insights into the shared molecular mechanisms of BCC and AK, revealing common pathways and potential therapeutic targets for developing novel treatment strategies and repurposing existing drugs for these prevalent skin cancers. Therefore, these findings may guide future research in understanding and developing targeted therapies for both conditions.