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

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

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 (n = 18) and those with non-recurrent (NR) and recurrent (R) cases of type I endometrioid (n = 24) and type II serous (n = 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 (AUCadj) of 0.914 (P < 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 AUCadjof 0.901 (P < 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.