Metabolomic Signature of Endometrial Cancer

Abstract

Endometrial cancer (EC) is the most common cancer of the female reproductive tract in developed countries. At the moment, no effective screening system is available. Here, we evaluate the diagnostic performance of a serum metabolomic signature. Two enrollments were carried out, one consisting of 168 subjects: 88 with EC and 80 healthy women, was used for building the classification models. The second (used to establish the performance of the classification algorithm) was consisted of 120 subjects: 30 with EC, 30 with ovarian cancer, 10 with benign endometrial disease, and 50 healthy controls. Two ensemble models were built, one with all EC versus controls (Model I) and one in which EC patients were aggregated according to their histotype (Model II). Serum metabolomic analysis was conducted via gas chromatography-mass spectrometry, while classification was done by an ensemble learning machine. Accuracy ranged from 62% to 99% for the Model I and from 67% to 100% for the Model II. Ensemble model showed an accuracy of 100% both for Model I and II. The most important metabolites in class separation were lactic acid, progesterone, homocysteine, 3-hydroxybutyrate, linoleic acid, stearic acid, myristic acid, threonine, and valine. The serum metabolomics signature of endometrial cancer patients is peculiar because it differs from that of healthy controls and from that of benign endometrial disease and from other gynecological cancers (such as ovarian cancer).

Prospective serum metabolomic profiling of lethal prostate cancer

“…Importantly, we observed a strong lipid‐dominant metabolomic profile of lethal metastatic disease, including elevated ketone bodies (BHBA), and acyl glycine/acyl carnitine, dicarboxylic and monohydroxy fatty acids, and lower serum lysophospholipid 1‐linoleoyl‐GPC (18:2). Alterations of BHBA potentially drive tumor progression and metastasis, and higher circulating BHBA has been associated with other cancers including liver, esophagus, ovary and endometrium . The higher circulating fatty acids we identified in cases with metastatic disease could indicate de novo biosynthesis or lipolytic triglyceride mobilization of fatty acids in response to the increased membrane lipid bilayer and cell proliferation requirements of these aggressive cancers .…”

“…Alterations of BHBA potentially drive tumor progression and metastasis, 36 and higher circulating BHBA has been associated with other cancers including liver, esophagus, ovary and endometrium. [37][38][39][40] The higher circulating fatty acids we identified in cases with metastatic disease could indicate de novo biosynthesis or lipolytic triglyceride mobilization of fatty acids in response to the increased membrane lipid bilayer and cell proliferation requirements of these aggressive cancers. [41][42][43] Upregulated fatty acid biosynthesis is also critical for increased acylcarnitine beta-oxidation for mitochondrial ATP production.…”

Blood Metabolites Associate with Prognosis in Endometrial Cancer

“…Several pathways have been suggested to be dysregulated in EC, including the lipid metabolism, by comparing cancer tissue samples with tissue from healthy controls [26]. Moreover, a distinct metabolomic signature of EC has been suggested by an Italian pilot study using different models [27]. A population-based case-control study also identified potential biomarkers in relation to EC which were independent of risk factors like obesity and previously known blood samples, and the authors suggest that metabolic profiling may be important in its early detection and risk assessment [28].…”

“…A diagnostic biomarker signature has also been proposed based on urine metabolomics profiling in EC [33]. A study among subjects with and without EC showed that the metabolic signature differed from both healthy controls, as well as from benign endometrial disease and other gynecological cancers [27].…”

Metabolomics of Physical Exercise: A Powerful Assessment Tool

“…A alanina e a tirosina foram identificadas como marcadores de idade em remadores, analisados em a 2 semanas consecutivas de treinamento 10 e o ácido lático, a progesterona, a homocisteína, o 3hidroxibutirato, o ácido linoleico, o ácido esteárico e a valina se mostraram potenciais biomarcadores para câncer do endométrio. 43 Maruyama et al Sugere que seja estudado a relação entre os fragmentos das titina, que são filamentos que mantém as estruturas dos sarcômeros, com as distrofias musculares, principalmente as causadas por doenças musculares quanto as provocadas por exercício físico e, também, o processo de recuperação. 44…”