Abstract
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 AUCadj of 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.
Highlights
Endometrial cancer (EC) is the sole gynecological neoplasm with a rising incidence and mortality and is currently the most common gynecological cancer in the United States, Canada, and other developed countries [1]
All individuals were selected from a larger cohort recruited at a single center [8], and pairing of NR cases with R cases was based on pathological and clinical (BMI and age) characteristics (Table 2; Table S1 Supplementary Material)
To the best of our knowledge, this is the first study reporting metabolites associated with type I and type II EC carcinomas and their recurrence following initial surgical treatment
Summary
Endometrial cancer (EC) is the sole gynecological neoplasm with a rising incidence and mortality and is currently the most common gynecological cancer in the United States, Canada, and other developed countries [1]. Type II neoplasms represent higher-grade tumors with a more aggressive clinical course, for which recurrence is more frequent and treatment remains a challenge [5]. Candidate diagnostic biomarkers such as CA125 and HE4 have been identified; their low sensitivity and/or specificity limit their use in the clinic [6, 7]. ECs are strongly associated with cumulative estrogen exposure, obesity, and other characteristics of metabolic syndrome [8,9,10,11,12] This does not apply only to type I carcinomas, as type II tumors can be associated with hormonal, reproductive, and metabolic factors [8]. Based on the recognition of the biological and prognostic differences between pathogenetic types of EC and given the poor prognosis for recurrent disease, it is critical to develop novel biomarkers
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