Identification of Novel Predictive Biomarkers for Endometrial Malignancies: <i>N</i>-Acylethanolamines



Ayakannu, Thangesweran ORCID: 0000-0002-7325-2327, Taylor, Anthony H, Marczylo, Timothy H, Maccarrone, Mauro and Konje, Justin C
(2019) Identification of Novel Predictive Biomarkers for Endometrial Malignancies: <i>N</i>-Acylethanolamines. FRONTIERS IN ONCOLOGY, 9 (JUN). 430-.

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Abstract

<b>Objective:</b> To identify new biochemical markers for endometrial cancer (EC). Recent evidence suggests that members of the endocannabinoid system (<i>N</i>-acylethanolamines) that bind to and activate receptors that are dysregulated in EC are involved in this tumour's biology. These observations suggest increased <i>N</i>-acylethanolamine levels in the tissue that might appear in plasma and could be used as disease biomarkers. <b>Methods:</b> <i>N</i>-arachidonoylethanolamine (anandamide, AEA) and the <i>N</i>-acylethanolamine substances, <i>N</i>-oleoylethanolamine (OEA), and <i>N</i>-palmitoylethanolamine (PEA) were quantified in plasma and endometrial tissue collected from 31 EC and seven atrophic controls using UHPLC-MS/MS. Receiver-operating characteristics (ROC) and logistic regression were used to determine diagnostic accuracy. Cannabinoid receptor 1 (CB1) and 2 (CB2) protein levels were determined by specific immunohistochemistry and histomorphometric analyses. Correlations between plasma and tissue levels of the three <i>N</i>-acylethanolamines and tissue levels of the three <i>N</i>-acylethanolamines and CB1 and CB2 receptor expression levels were determined using correlation analysis. <b>Results:</b> Plasma and tissue AEA and PEA levels were significantly (<i>p</i> < 0.05) higher in EC than controls whilst OEA levels were significantly elevated in type 1 EC tissues but not in plasma. There were significant positive correlations between plasma and tissue levels of AEA (<i>R</i> <sup>2</sup> = 0.302, <i>p</i> = 0.008) and PEA (<i>R</i> <sup>2</sup> = 0.182, <i>p</i> = 0.047), but not for OEA (<i>R</i> <sup>2</sup> = 0.022, <i>p</i> = 0.506). The diagnostic accuracies for EC were: sensitivity of 53.3%, specificity of 100% for plasma AEA (>1.36 nM); sensitivity of 73.3%, specificity of 100% for plasma PEA (>27.5 nM); and sensitivity of 93.3%, specificity of 28.6% for plasma OEA (>4.97 nM). Logistic regression increased the area under the ROC curve (AUC) from 0.781 for AEA, 0.857 for PEA, and 0.543 for OEA to a combined AUC of 0.933 for EC diagnosis. Significant inverse correlations between tissue AEA (<i>R</i> <sup>2</sup> = 0.343, <i>p</i> = 0.003) and PEA (<i>R</i> <sup>2</sup> = 0.384, <i>p</i> < 0.0001) levels and CB1 expression were observed. No correlation between tissue levels of OEA and CB1 and tissue levels of any of the three <i>N</i>-acylethanolamines and CB2 protein expression were observed, except in the type 1 EC patients. <b>Conclusion:</b> Since plasma AEA and PEA are significantly elevated in patients with EC and a reflection of production by the endometrial tumour, then these lipids have the potential to be useful biomarkers for the early diagnosis of EC.

Item Type: Article
Uncontrolled Keywords: anandamide, biomarker, endocannabinoid, endometrial cancer, prediction
Depositing User: Symplectic Admin
Date Deposited: 11 May 2020 10:39
Last Modified: 01 Feb 2024 08:21
DOI: 10.3389/fonc.2019.00430
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3086393