Identification of metabolomic biomarkers for endometrial cancer and its recurrence after surgery in postmenopausal women

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

doi:10.1016/j.dmpk.2018.09.115

Cited by 6 publications

(12 citation statements)

References 58 publications

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“…Our finding that glycerophospholipids are important diagnostic biomarkers in endometrial cancer is consistent with published data [ 39 , 40 , 41 , 42 ]. Glycerophospholipids are the main components of biological membranes and, alongside fatty acids, glycerolipids, sphingolipids and sterols, have been linked to cancer development [ 43 ].…”

Section: Discussionsupporting

confidence: 93%

“…Trousil and colleagues found that altered choline metabolism in endometrial cancer is caused by an overexpression of choline kinase alpha and hyperactivation of the deacylation pathway [ 48 ]. Choline derivatives are detectable in blood, tumour and vaginal fluid in women with endometrial cancer [ 39 , 40 , 41 ]. They have also been described in breast, prostate and other solid tumours [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…Knapp and colleagues found sphinganine, sphingosine, dihydroceramide and ceramide levels to be significantly elevated in endometrial cancer tissue compared to healthy endometrium [ 56 ]. Audet-Delage and colleagues reported sphingolipids to be significantly elevated in the serum of women with recurrent non-endometrioid endometrial cancer [ 39 ]. Sphingolipids are involved in inflammation, proliferation, cell migration and apoptosis [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…These results must be interpreted with caution given the small sample sizes. Heme, an iron-containing porphyrin, is an important source of electrons for electron transfer and has been shown to be elevated in the clinically aggressive type II endometrial cancer [ 39 , 58 ]. Homovanillate, a metabolite of dopamine, is a neurotransmitter originating from tyrosine [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

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Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer

Njoku

Campbell

Geary

et al. 2021

Cancers

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Endometrial cancer is the most common malignancy of the female genital tract and a major cause of morbidity and mortality in women. Early detection is key to ensuring good outcomes but a lack of minimally invasive screening tools is a significant barrier. Most endometrial cancers are obesity-driven and develop in the context of severe metabolomic dysfunction. Blood-derived metabolites may therefore provide clinically relevant biomarkers for endometrial cancer detection. In this study, we analysed plasma samples of women with body mass index (BMI) ≥30kg/m2 and endometrioid endometrial cancer (cases, n = 67) or histologically normal endometrium (controls, n = 69), using a mass spectrometry-based metabolomics approach. Eighty percent of the samples were randomly selected to serve as a training set and the remaining 20% were used to qualify test performance. Robust predictive models (AUC > 0.9) for endometrial cancer detection based on artificial intelligence algorithms were developed and validated. Phospholipids were of significance as biomarkers of endometrial cancer, with sphingolipids (sphingomyelins) discriminatory in post-menopausal women. An algorithm combining the top ten performing metabolites showed 92.6% prediction accuracy (AUC of 0.95) for endometrial cancer detection. These results suggest that a simple blood test could enable the early detection of endometrial cancer and provide the basis for a minimally invasive screening tool for women with a BMI ≥ 30 kg/m2.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer

Njoku

Campbell

Geary

et al. 2021

Cancers

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“…Metabolomics is a powerful high-throughput approach to identify metabolites or metabolic signatures that are associated with disease development and could help identify novel biological mechanisms involved in pathogenesis [12][13][14][15][16][17]. Currently, few epidemiologic studies have investigated the association between circulating metabolites of major biochemical classes and subsequent risk of endometrial cancer, and all were case-control studies of small sample size with blood samples collected after diagnosis [18][19][20][21][22]. To address these gaps in the literature, we performed a targeted metabolomic study in pre-diagnostic blood samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC).…”

Section: Introductionmentioning

confidence: 99%

Prospective analysis of circulating metabolites and endometrial cancer risk

Dossus

Kouloura

Biessy

et al. 2021

Gynecologic Oncology

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Background. Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods. A total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed.Results. After adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR 1SD : 1.18, 95% CI: 1.05-1.33), and glycine, serine, and free carnitine (C0) were inversely (OR 1SD : 0.89, 95% CI: 0.80-0.99; OR 1SD : 0.89, 95% CI: 0.79-1.00 and OR 1SD : 0.91, 95% CI: 0.81-1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR 1SD : 1.14, 95% CI: 1.02-1.28) and that of short chain to free acylcarnitines (OR 1SD : 1.12, 95% CI: 1.00-1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results.Conclusion. These findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.

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