Ray O Bahado-Singh1, Amit Lugade2, Jayson Field3, Zaid Al-Wahab3, BeomSoo Han4, Rupasri Mandal4, Trent C Bjorndahl4, Onur Turkoglu5, Stewart F Graham5, David Wishart4,6, Kunle Odunsi2,7. 1. Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI, 48073, USA. Ray.bahado-singh@beaumont.org. 2. Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA. 3. Department of Gynecologic Oncology, William Beaumont Health, Royal Oak, MI, USA. 4. Departments of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E8, Canada. 5. Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI, 48073, USA. 6. Department of Computing Sciences, University of Alberta, Edmonton, AB, T6G 2E8, Canada. 7. Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Abstract
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.
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.
Entities:
Keywords:
Biomarker; Endometrial cancer; Mass spectrometry; Metabolomics; Nuclear magnetic resonance
Authors: David B Liesenfeld; Nina Habermann; Robert W Owen; Augustin Scalbert; Cornelia M Ulrich Journal: Cancer Epidemiol Biomarkers Prev Date: 2013-10-04 Impact factor: 4.254
Authors: Anne Cathrine Staff; Jone Trovik; Ane Gerda Zahl Eriksson; Elisabeth Wik; Kai C Wollert; Tibor Kempf; Helga B Salvesen Journal: Clin Cancer Res Date: 2011-05-26 Impact factor: 12.531
Authors: P A Vorkas; J Shalhoub; M R Lewis; K Spagou; E J Want; J K Nicholson; A H Davies; E Holmes Journal: Eur J Vasc Endovasc Surg Date: 2016-05-23 Impact factor: 7.069
Authors: Kunle Odunsi; Robert M Wollman; Christine B Ambrosone; Alan Hutson; Susan E McCann; Jonathan Tammela; John P Geisler; Gregory Miller; Thomas Sellers; William Cliby; Feng Qian; Bernadette Keitz; Marilyn Intengan; Shashikant Lele; James L Alderfer Journal: Int J Cancer Date: 2005-02-20 Impact factor: 7.396
Authors: Kelechi Njoku; Amy E Campbell; Bethany Geary; Michelle L MacKintosh; Abigail E Derbyshire; Sarah J Kitson; Vanitha N Sivalingam; Andrew Pierce; Anthony D Whetton; Emma J Crosbie Journal: Cancers (Basel) Date: 2021-02-10 Impact factor: 6.575
Authors: Jacopo Troisi; Antonio Mollo; Martina Lombardi; Giovanni Scala; Sean M Richards; Steven J K Symes; Antonio Travaglino; Daniele Neola; Umberto de Laurentiis; Luigi Insabato; Attilio Di Spiezio Sardo; Antonio Raffone; Maurizio Guida Journal: Biomolecules Date: 2022-09-02
Authors: Jacopo Troisi; Antonio Raffone; Antonio Travaglino; Gaetano Belli; Carmen Belli; Santosh Anand; Luigi Giugliano; Pierpaolo Cavallo; Giovanni Scala; Steven Symes; Sean Richards; David Adair; Alessio Fasano; Vincenzo Bottigliero; Maurizio Guida Journal: JAMA Netw Open Date: 2020-09-01