Metabolomic prediction of endometrial cancer.

Ray O Bahado-Singh, Beaumont Health
Amit Lugade
Jayson Field, Beaumont Health
Zaid Al-Wahab, Beaumont Health
BeomSoo Han
Rupasri Mandal
Trent C Bjorndahl
Onur Turkoglu, Beaumont Health
Stewart F Graham, Beaumont Health
David Wishart
Kunle Odunsi


INTRODUCTION: Endometrial cancer (EC) is associated with metabolic disturbances including obesity, diabetes and metabolic syndrome. Identifying metabolite biomarkers for EC detection has a crucial role in reducing morbidity and mortality.

OBJECTIVE: To determine whether metabolomic based biomarkers can detect EC overall and early-stage EC.

METHODS: We performed NMR and mass spectrometry based metabolomic analyses of serum in EC cases versus controls. A total of 46 early-stage (FIGO stages I-II) and 10 late-stage (FIGO stages III-IV) EC cases constituted the study group. A total of 60 unaffected control samples were used. Patients and controls were divided randomly into a discovery group (n = 69) and an independent validation group (n = 47). Predictive algorithms based on biomarkers and demographic characteristics were generated using logistic regression analysis.

RESULTS: A total of 181 metabolites were evaluated. Extensive changes in metabolite levels were noted in the EC versus the control group. The combination of C14:2, phosphatidylcholine with acyl-alkyl residue sum C38:1 (PCae C38:1) and 3-hydroxybutyric acid had an area under the receiver operating characteristics curve (AUC) (95% CI) = 0.826 (0.706-0.946) and a sensitivity = 82.6%, and specificity = 70.8% for EC overall. For early EC prediction: BMI, C14:2 and PC ae C40:1 had an AUC (95% CI) = 0.819 (0.689-0.95) and a sensitivity = 72.2% and specificity = 79.2% in the validation group.

CONCLUSIONS: EC is characterized by significant perturbations in important cellular metabolites. Metabolites accurately detected early-stage EC cases and EC overall which could lead to the development of non-invasive biomarkers for earlier detection of EC and for monitoring disease recurrence.