Cancer and
arachidonic acid (AA) have important linkages. For example, AA metabolites regulate several critical
biological functions associated with
carcinogenesis: angiogenesis, apoptosis, and
cancer invasion. However, little is known about the comparative changes in metabolite expression of the
arachidonic acid pathway (
AAP) in
carcinogenesis. In this study, we examined transcriptome data from 12
cancers, such as breast invasive
carcinoma,
colon adenocarcinoma,
lung adenocarcinoma, and prostate
adenocarcinoma. We also report here a reverse-engineering strategy wherein we estimated metabolic signatures associated with
AAP by (1) making deductive inferences through transcriptome-level data extraction, (2) remodeling AA metabolism, and (3) performing a comparative analysis of
cancer types to determine the similarities and differences between different
cancer types with respect to AA metabolic alterations. We identified 77
AAP gene signatures differentially expressed in
cancers and 37
AAP metabolites associated with them. Importantly, the metabolite 15(S)-HETE was identified in almost all
cancers, while arachidonate,
5-HETE, PGF2α,
14,15-EET,
8,9-EET,
5,6-EET, and
20-HETE were discovered as other most regulated metabolites. This study shows that the 12
cancers studied herein, although in different branches of the
AAP, have altered expression of
AAP gene signatures. Going forward, AA related-
cancer research generally, and the molecular signatures and their estimated metabolites reported herein specifically, hold broad promise for precision/
personalized medicine in oncology as potential therapeutic and diagnostic targets.