TY - JOUR
T1 - Targeted metabolomic profiling of low and high grade serous epithelial ovarian cancer tissues
T2 - a pilot study
AU - Garg, Gunjal
AU - Yilmaz, Ali
AU - Kumar, Praveen
AU - Turkoglu, Onur
AU - Mutch, David G.
AU - Powell, Matthew A.
AU - Rosen, Barry
AU - Bahado-Singh, Ray O.
AU - Graham, Stewart F.
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Introduction: Epithelial ovarian cancer (EOC) remains the leading cause of death from gynecologic malignancies and has an alarming global fatality rate. Besides the differences in underlying pathogenesis, distinguishing between high grade (HG) and low grade (LG) EOC is imperative for the prediction of disease progression and responsiveness to chemotherapy. Objectives: The aim of this study was to investigate, the tissue metabolome associated with HG and LG serous epithelial ovarian cancer. Methods: A combination of one dimensional proton nuclear magnetic resonance (1D H NMR) spectroscopy and targeted mass spectrometry (MS) was employed to profile the tissue metabolome of HG, LG serous EOCs, and controls. Results: Using partial least squares-discriminant analysis, we observed significant separation between all groups (p < 0.05) following cross validation. We identified which metabolites were significantly perturbed in each EOC grade as compared with controls and report the biochemical pathways which were perturbed due to the disease. Among these metabolic pathways, ascorbate and aldarate metabolism was identified, for the first time, as being significantly altered in both LG and HG serous cancers. Further, we have identified potential biomarkers of EOC and generated predictive algorithms with AUC (CI) = 0.940 and 0.929 for HG and LG, respectively. Conclusion: These previously unreported biochemical changes provide a framework for future metabolomic studies for the development of EOC biomarkers. Finally, pharmacologic targeting of the key metabolic pathways identified herein could lead to novel and effective treatments of EOC.
AB - Introduction: Epithelial ovarian cancer (EOC) remains the leading cause of death from gynecologic malignancies and has an alarming global fatality rate. Besides the differences in underlying pathogenesis, distinguishing between high grade (HG) and low grade (LG) EOC is imperative for the prediction of disease progression and responsiveness to chemotherapy. Objectives: The aim of this study was to investigate, the tissue metabolome associated with HG and LG serous epithelial ovarian cancer. Methods: A combination of one dimensional proton nuclear magnetic resonance (1D H NMR) spectroscopy and targeted mass spectrometry (MS) was employed to profile the tissue metabolome of HG, LG serous EOCs, and controls. Results: Using partial least squares-discriminant analysis, we observed significant separation between all groups (p < 0.05) following cross validation. We identified which metabolites were significantly perturbed in each EOC grade as compared with controls and report the biochemical pathways which were perturbed due to the disease. Among these metabolic pathways, ascorbate and aldarate metabolism was identified, for the first time, as being significantly altered in both LG and HG serous cancers. Further, we have identified potential biomarkers of EOC and generated predictive algorithms with AUC (CI) = 0.940 and 0.929 for HG and LG, respectively. Conclusion: These previously unreported biochemical changes provide a framework for future metabolomic studies for the development of EOC biomarkers. Finally, pharmacologic targeting of the key metabolic pathways identified herein could lead to novel and effective treatments of EOC.
KW - H NMR
KW - Metabolomics
KW - Multivariate data analysis
KW - Serous ovarian cancer
KW - Targeted mass spectrometry
UR - http://www.scopus.com/inward/record.url?scp=85057205066&partnerID=8YFLogxK
U2 - 10.1007/s11306-018-1448-3
DO - 10.1007/s11306-018-1448-3
M3 - Article
C2 - 30830441
AN - SCOPUS:85057205066
SN - 1573-3882
VL - 14
JO - Metabolomics
JF - Metabolomics
IS - 12
M1 - 154
ER -