Plasma endocannabinoids as potential biomarkers for endometrial cancer


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Thangesweran Ayakannu1, Anthony Taylor1, Timothy Marczylo2, Jonathan Willets1, Quentin Davies3, Laurence Brown4, Esther Moss3, Justin Konje1
1Reproductive Sciences Section, department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK, 2Centre for Radiation, Chemical and Environtment Hazards, Public Health England, Harwell Campus, Oxfordshire, UK, Oxfordshire, UK, 3University Hospitals of Leicester NHS Trust, Gynaecology Oncology Department, Leicester, UK, 4University Hospitals of Leicester NHS Trust, Pathology Department, Leicester, UK

Background

Presently, there are no validated plasma biomarkers for the detection of endometrial cancer. Recently, a relationship between endocannabinoids and oestrogen has been identified because oestrogen appears to regulate both the endocannabinoid system in physiological and pathological states as well as the natural progression of endometrial cancer. Therefore it has been proposed that endocannabinoids may play an important role in the aetiopathology of endometrial cancer. To investigate a potential role of endocannabinoids as biomarkers in endometrial cancer, tissue and plasma levels of three endocannabinoids were evaluated.

Method

The endocannabinoids, N-arachidonoylethanolamine (AEA), N-oleyolethanolamine (OEA) and N-palmitoylethanolamine (PEA) were extracted from whole blood and endometrial tissues collected from women with type 1 (endometrioid adenocarcinoma) and type 2 (serous and carcinosarcoma) and an age-matched atrophic control group and quantified using UHPLC-tandem mass spectrometry against authentic standards. Plasma measurement for AEA, OEA and PEA were obtained from atrophic age-matched (n=6) and endometrial cancer n=15, whereas, for tissue levels, n=6 (atrophic) and n=28 (endometrial cancer).

Results

AEA and PEA levels in plasma and tissues of endometrial cancer patients were significantly (P<0.05; Student's t-test) higher when compared to the control group, whilst OEA was unaffected in both tissue and plasma. Furthermore, there was a significant correlation (r2=0.28 and P<0.0412 for AEA; r2=0.304 and P=<0.048 for PEA) between plasma and tissue AEA and PEA levels, but no relationship was observed for OEA.

Conclusion

These data suggest a potential vital role for AEA and PEA in the aetiopathology of endometrial cancer. The close correlation between plasma and tissue AEA and PEA, but not OEA suggest that both former molecules could be used as biomarkers for disease. Additionally, the endocannabinoid system thus presents an attractive novel target for pharmacological intervention in the fight against endometrial cancer.