Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0476089 (
endometrial cancer
)
11,379
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Objective:
To identify new biochemical markers for
endometrial cancer
(EC). Recent evidence suggests that members of the endocannabinoid system (
N
-acylethanolamines) that bind to and activate receptors that are dysregulated in EC are involved in this tumour's biology. These observations suggest increased
N
-acylethanolamine levels in the tissue that might appear in plasma and could be used as disease biomarkers.
Methods:
N
-arachidonoylethanolamine (anandamide, AEA) and the
N
-acylethanolamine substances,
N
-oleoylethanolamine (OEA), and
N
-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
N
-acylethanolamines and tissue levels of the three
N
-acylethanolamines and
CB1
and CB2 receptor expression levels were determined using correlation analysis.
Results:
Plasma and tissue AEA and PEA levels were significantly (
p
< 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 (
R
2
= 0.302,
p
= 0.008) and PEA (
R
2
= 0.182,
p
= 0.047), but not for OEA (
R
2
= 0.022,
p
= 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 (
R
2
= 0.343,
p
= 0.003) and PEA (
R
2
= 0.384,
p
< 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
N
-acylethanolamines and CB2 protein expression were observed, except in the type 1 EC patients.
Conclusion:
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.
...
PMID:Identification of Novel Predictive Biomarkers for Endometrial Malignancies:
N
-Acylethanolamines. 3124 82
