Integrated eicosanoid lipidomics and gene expression reveal decreased prostaglandin catabolism and increased 5-lipoxygenase expression in aggressive subtypes of endometrial cancer

The Journal of Pathology
Michele CummingsNicolas M Orsi

Abstract

Eicosanoids comprise a diverse group of bioactive lipids which orchestrate inflammation, immunity, and tissue homeostasis, and whose dysregulation has been implicated in carcinogenesis. Among the various eicosanoid metabolic pathways, studies of their role in endometrial cancer (EC) have very much been confined to the COX-2 pathway. This study aimed to determine changes in epithelial eicosanoid metabolic gene expression in endometrial carcinogenesis; to integrate these with eicosanoid profiles in matched clinical specimens; and, finally, to investigate the prognostic value of candidate eicosanoid metabolic enzymes. Eicosanoids and related mediators were profiled using liquid chromatography-tandem mass spectrometry in fresh frozen normal, hyperplastic, and cancerous (types I and II) endometrial specimens (n = 192). Sample-matched epithelia were isolated by laser capture microdissection and whole genome expression analysis was performed using microarrays. Integration of eicosanoid and gene expression data showed that the accepted paradigm of increased COX-2-mediated prostaglandin production does not apply in EC carcinogenesis. Instead, there was evidence for decreased PGE2 /PGF2α inactivation via 15-hydroxyprostaglandin dehydroge...Continue Reading

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Citations

Nov 13, 2018·Molecular Reproduction and Development·Daniela Paes de Almeida Ferreira BragaEdson Guimarães Lo Turco
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Sep 4, 2021·Cancer Chemotherapy and Pharmacology·Liling LiShaoshuai Wang

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