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Metabolomics of biomarker discovery in ovarian cancer: a systematic review of the current literature

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Abstract

Introduction

Metabolomics is the emerging member of “omics” sciences advancing the understanding, diagnosis and treatment of many cancers, including ovarian cancer (OC).

Objectives

To systematically identify the metabolomic abnormalities in OC detection, and the dominant metabolic pathways associated with the observed alterations.

Methods

An electronic literature search was performed, up to and including January 15th 2016, for studies evaluating the metabolomic profile of patients with OC compared to controls. QUADOMICS tool was used to assess the quality of the twenty-three studies included in this systematic review.

Results

Biological samples utilized for metabolomic analysis include: serum/plasma (n = 13), urine (n = 4), cyst fluid (n = 3), tissue (n = 2) and ascitic fluid (n = 1). Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in OC. Increased levels of tricarboxylic acid cycle intermediates and altered metabolites of the glycolytic pathway pointed to perturbations in cellular respiration. Alterations in lipid metabolism included enhanced fatty acid oxidation, abnormal levels of glycerolipids, sphingolipids and free fatty acids with common elevations of palmitate, oleate, and myristate. Increased levels of glutamine, glycine, cysteine and threonine were commonly reported while enhanced degradations of tryptophan, histidine and phenylalanine were found. N-acetylaspartate, a brain amino acid, was found elevated in primary and metastatic OC tissue and ovarian cyst fluid. Further, elevated levels of ketone bodies including 3-hydroxybutyrate were commonly reported. Increased levels of nucleotide metabolites and tocopherols were consistent through out the studies.

Conclusion

Metabolomics presents significant new opportunities for diagnostic biomarker development, elucidating previously unknown mechanisms of OC pathogenesis.

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Acknowledgments

The authors would like to acknowledge the medical librarian of Beaumont Hospital, Donna Marshall, for her contribution in extensive literature search and Dr. David Timson of Queen’s University Belfast for supplying the protein image of UDP-galactose 4′-epimerase bound to its cofactor and substrate. Special gratitude is also extended to Rose Callahan for her input in manuscript editing. This work was supported by NIH 5T32 CA 108456 (to JBS), Roswell Park Alliance Foundation (to KO) and RPCI-UPCI Ovarian Cancer SPORE P50CA159981-01A1 (to KO).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Beaumont Hospital, 3601 W. 13 Mile Rd., Royal Oak, MI, 48073, USA

    Onur Turkoglu, Amna Zeb, Stewart Graham & Ray Bahado-Singh

  2. Department of Chemistry, College of Arts and Sciences, University at Buffalo, Buffalo, NY, USA

    Thomas Szyperski

  3. Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA

    J. Brian Szender & Kunle Odunsi

  4. Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY, USA

    Kunle Odunsi

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Correspondence to Onur Turkoglu.

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Onur Turkoglu, Amna Zeb, Stewart Graham, Thomas Szyperski, J Brian Szender, Kunle Odunsi and Ray Bahado-Singh declare that they have no conflict of interest.

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Turkoglu, O., Zeb, A., Graham, S. et al. Metabolomics of biomarker discovery in ovarian cancer: a systematic review of the current literature. Metabolomics 12, 60 (2016). https://doi.org/10.1007/s11306-016-0990-0

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  • Published:

  • DOI: https://doi.org/10.1007/s11306-016-0990-0

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