AUTHOR=Audet-Delage Yannick , Villeneuve Lyne , Grégoire Jean , Plante Marie , Guillemette Chantal 

TITLE=Identification of Metabolomic Biomarkers for Endometrial Cancer and Its Recurrence after Surgery in Postmenopausal Women

JOURNAL=Frontiers in Endocrinology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2018.00087

DOI=10.3389/fendo.2018.00087

ISSN=1664-2392

ABSTRACT=<p>Endometrial cancer (EC) is the most frequent gynecological cancer in developed countries. Most EC occurs after menopause and is diagnosed as endometrioid (type I) carcinomas, which exhibit a favorable prognosis. In contrast, non-endometrioid (type II) carcinomas such as serous tumors have a poor prognosis. Our goal was to identify novel blood-based markers associated with EC subtypes and recurrence after surgery in postmenopausal women. Using mass spectrometry-based untargeted metabolomics, we examined preoperative serum metabolites among control women (<italic>n</italic> = 18) and those with non-recurrent (NR) and recurrent (R) cases of type I endometrioid (<italic>n</italic> = 24) and type II serous (<italic>n</italic> = 12) carcinomas. R and NR cases were similar with respect to pathological characteristics, body mass index, and age. A total of 1,592 compounds were analyzed including 14 different lipid classes. When we compared EC cases with controls, 137 metabolites were significantly different. A combination of spermine and isovalerate resulted in an age-adjusted area under the receiver-operating characteristic curve (AUC<sub>adj</sub>) of 0.914 (<italic>P</italic> &lt; 0.001) for EC detection. The combination of 2-oleoylglycerol and TAG42:2-FA12:0 allowed the distinction of R cases from NR cases with an AUC<sub>adj</sub> of 0.901 (<italic>P</italic> &lt; 0.001). Type I R cases were also characterized by much lower levels of bile acids and elevated concentrations of phosphorylated fibrinogen cleavage peptide, whereas type II R cases displayed higher levels of ceramides. The findings from our pilot study provide a detailed metabolomics study of EC and identify putative serum biomarkers for defining clinically relevant risk groups.</p>