Aspirin and cancer survival-related pathways: a review and analysis of molecular mechanisms

Abstract Background: The benefit of aspirin on cancer survival is debated. Data from randomized clinical trials and cohort studies are discordant, although meta-analysis shows a clear survival advantage when aspirin is added to the standard of care. However, the mechanism by which aspirin improves cancer survival is not clear. Methods: A PubMed search was carried out to identify articles reporting genes and pathways associated with aspirin and cancer survival. Gene ontology and pathway enrichment analysis was carried out using web-based tools. Gene-gene and protein-protein interactions were evaluated. Crosstalk between pathways was identified and plotted. Results: Forty-one genes were identified and classified into primary genes (PTGS2 and PTGES2), genes regulating cellular proliferation, interleukin and cytokine genes and DNA repair genes. The network analysis showed a rich gene-gene and protein-protein interaction between these genes and proteins. Pathway enrichment showed the interleukin and cellular transduction pathways as the main pathways involved in aspirin-related survival, in addition to DNA repair, autophagy, extracellular matrix, and apoptosis pathways. Crosstalk of PTGS2 with EGFR, JAK/AKT, TP53, interleukin/TNFα/NFκB, GSK3B/BRCA/PARP, CXCR/MUC1, and WNT/CTNNB pathways was identified. Conclusions: The results of present study demonstrate that aspirin improves cancer survival by the interplay of 41 genes through a complex mechanism. PTGS2 is the primary target of aspirin and impacts cancer survival through 6 primary pathways: the interleukin pathway, extracellular matrix pathway, signal transduction pathway, apoptosis pathway, autophagy pathway and DNA repair pathway.