The deregulation of arachidonic acid metabolism in ovarian cancer

Abstract

Arachidonic acid (AA) is a crucial polyunsaturated fatty acid in the human body, metabolized through the pathways of COX, LOX, and cytochrome P450 oxidase to generate various metabolites. Recent studies have indicated that AA and its metabolites play significant regulatory roles in the onset and progression of ovarian cancer. This article examines the recent research advancements on the correlation between AA metabolites and ovarian cancer, both domestically and internationally, suggesting their potential use as biological markers for early diagnosis, targeted therapy, and prognosis monitoring.

Keywords: arachidonic acid; biological marker; metabolic pathway; ovarian cancer; targeted therapy.

Figure 1

Overview of the three pathways for AA metabolism in cancer. Upon cell stimulation, phospholipase A2 induces FFAs, primarily AA derived from the lipid bilayer. The released AA is metabolized into bioactive lipid signaling molecules by three different enzymatic pathways. COX-1/2 metabolize AA to a series of prostaglandins (PGD2, PGE2, PGF2, PGH2, and PGI2).5-LO metabolizes AA to 5-HETE, LTB4, and cysteine leukotrienes, and 12-LO metabolizes AA to 12-HETE. Both subtypes of 15-LO metabolize AA to 15-HETE and, to a lesser extent, 12-HETE. Cytochrome P450 metabolizes AA to 19-/20-HETEand so on.

Figure 2

Overview of the pathways for the COX-mediated AA metabolism in cancer.

Figure 3

Overview of the pathways for the LOX-mediated AA metabolism in cancer.

Figure 4

Overview of the pathways for the CYP450-mediated AA metabolism in cancer.

Figure 5

Functional and signaling pathway enrichment analysis of AA metabolism related genes in OC. (A) Volcano plot of DEGs between ovarian cancer and non-tumor tissues based on the TCGA (OV for ovarian cancer, accessed on 20240329) and GTEx (Ovary, accessed on 20240329) database. (B) Venn diagram showing the number of DEGs and AA metabolism related genes; the intersection part is the total number of genes in the two datasets. (C) Results of GO analysis of overlapping DEGs. (D, E) Forest plot demonstrating the univariate Cox model results of 34 OS/PFS-related key genes of AA metabolism.