Abstract
Endometrial cancer has a high prevalence among post-menopausal women in developed countries. We aimed to explore whether certain metabolic patterns could be related to the characteristics of aggressive disease and poorer survival among endometrial cancer patients in Western Norway. Patients with endometrial cancer with short survival (n = 20) were matched according to FIGO (International Federation of Gynecology and Obstetrics, 2009 criteria) stage, histology, and grade, with patients with long survival (n = 20). Plasma metabolites were measured on a multiplex system including 183 metabolites, which were subsequently determined using liquid chromatography-mass spectrometry. Partial least square discriminant analysis, together with hierarchical clustering, was used to identify patterns which distinguished short from long survival. A proposed signature of metabolites related to survival was suggested, and a multivariate receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.820–0.965 (p ≤ 0.001). Methionine sulfoxide seems to be particularly strongly associated with poor survival rates in these patients. In a subgroup with preoperative contrast-enhanced computed tomography data, selected metabolites correlated with the estimated abdominal fat distribution parameters. Metabolic signatures may predict prognosis and be promising supplements when evaluating phenotypes and exploring metabolic pathways related to the progression of endometrial cancer. In the future, this may serve as a useful tool in cancer management.
Highlights
Endometrial cancer (EC) is one of the most prevalent cancers among women in Western countries, typically occurring after menopause, and having an increased incidence with advancing age, overweight and obesity [1,2]
Biomarkers have been proposed for application in cervical and ovarian cancers based on metabolomics [18,19,20,21,22,23,24,25]
20 patients with long survival were matched with those having short survival for FIGO stage, histology, grade, age, body mass index (BMI), and parity, and were selected for the analyses
Summary
Endometrial cancer (EC) is one of the most prevalent cancers among women in Western countries, typically occurring after menopause, and having an increased incidence with advancing age, overweight and obesity [1,2]. This type of gynecological malignancy most frequently presents as endometrioid. EC includes high-grade variants, like serous and clear-cell carcinomas, and often has a poorer prognosis. Cancer cells have impaired energy metabolism, and metabolic intermediates typically accumulate in tumors [3]. Whereas an altered glucose metabolism is a well-recognized feature of cancer cells, shifts involving fatty acid (FA) metabolism have more recently come into focus and, as opposed to in healthy cells, de novo FA synthesis frequently occurs in cancer cells [3]
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