Blood Metabolites Associate with Prognosis in Endometrial Cancer

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.

Metabolomics for Diagnosis and Prognosis of Uterine Diseases? A Systematic Review

“…Alterations of a series of lipid metabolites were reported for tissue and blood samples, including glycerophospholipids, lysophospholipids, sphingolipids, fatty acids, acylcarnitines, prostaglandin metabolites, and steroid hormones [ 81 , 83 , 84 , 92 , 93 , 94 , 95 , 96 ]. In serum and plasma samples, glycerophospholipids in combination with other metabolites showed diagnostic and prognostic potential [ 81 , 82 , 96 ], while changes in the profiles of these metabolites in EC tissue were associated with tumor progression [ 93 ]. Also, sphingolipids [ 81 , 84 ] and acylcarnitines [ 81 , 82 , 84 , 96 ] revealed diagnostic and prognostic potential.…”

“…In serum and plasma samples, glycerophospholipids in combination with other metabolites showed diagnostic and prognostic potential [ 81 , 82 , 96 ], while changes in the profiles of these metabolites in EC tissue were associated with tumor progression [ 93 ]. Also, sphingolipids [ 81 , 84 ] and acylcarnitines [ 81 , 82 , 84 , 96 ] revealed diagnostic and prognostic potential. Good diagnostic accuracy to distinguish between EC and healthy women was reported for a model that included serum lactic acid, homocysteine, 3-hydroxybutyrate, linoleic acid, stearic acid, myristic acid, threonine, valine, and progesterone [ 83 ].…”

“…These models included a series of plasma metabolites, as phosphatidylcholines, acylcarnitines, lysophosphatidylcholines, aspartic acid, and several low molecular weight metabolites (i.e. ; serotonin, spermine, spermidine, dimethylarginine, hexose, methionine sulfoxide) [ 82 ]. Our recent study revealed that alterations in metabolic profiles allow pre-operative prognosis of lymphovascular invasion, which is considered one of the main prognostic factors [ 81 ].…”

Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review

“…In the studies on gynecological cancer, the most prevalent technique for the study of free amino acid alterations is LC-MS. Thirty-one out of forty-four reviewed articles employed different types of LC-MS systems, six of them employed GC-MS, whereas proton nuclear magnetic resonance ( 1 H-NMR) was used in seven studies ( Table 1 ). Other analytical approaches used in metabolomics research included in this review included flow-injection mass spectrometry [ 11 , 14 , 16 , 23 , 30 , 32 , 34 , 42 , 46 ] and direct analysis in real-time mass spectrometry [ 20 ].…”

Metabolomic Biomarkers for Detection, Prognosis and Identifying Recurrence in Endometrial Cancer

“…Strand and colleagues reported methionine sulfoxide to be strongly associated with poor survival in a study of 40 cases of EC [111]. They proposed a prognostic signature of metabolites found to have an AUC of 0.82-0.98 for EC survival (p < 0.001).…”