Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Metabolomic Biomarkers in Gynecology: A Treasure Path or a False Path?

Author(s): Igor Govorov *, Stanislav Sitkin , Tatyana Pervunina , Alexey Moskvin , Denis Baranenko and Eduard Komlichenko

Volume 27, Issue 22, 2020

Page: [3611 - 3622] Pages: 12

DOI: 10.2174/0929867326666190104124245

Price: $65


Omic-technologies (genomics, transcriptomics, proteomics and metabolomics) have become more important in current medical science. Among them, it is metabolomics that most accurately reflects the minor changes in body functioning, as it focuses on metabolome – the group of the metabolism products, both intermediate and end. Therefore, metabolomics is actively engaged in fundamental and clinical studies and search for potential biomarkers. The biomarker could be used in diagnostics, management and stratification of the patients, as well as in prognosing the outcomes. The good example is gynecology, since many gynecological diseases lack effective biomarkers. In the current review, we aimed to summarize the results of the studies, devoted to the search of potential metabolomic biomarkers for the most common gynecological diseases.

Keywords: Metabolomics, biomarkers, gynecology, uterine cervical neoplasms, ovarian neoplasms, endometriosis, polycystic ovary syndrome, leiomyoma.

Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[] [PMID: 30207593]
Arbyn, M.; Anttila, A.; Jordan, J.; Ronco, G.; Schenck, U.; Segnan, N.; Wiener, H.; Herbert, A.; von Karsa, L. European guidelines for quality assurance in cervical cancer screening . Second edition--summary document Ann. Oncol.,; , 2010. 21(3), 448-458
[] [PMID: 20176693]
Yin, M.Z.; Tan, S.; Li, X.; Hou, Y.; Cao, G.; Li, K.; Kou, J.; Lou, G. Identification of phosphatidylcholine and lysophosphatidylcholine as novel biomarkers for cervical cancers in a prospective cohort study. Tumour Biol., 2016, 37(4), 5485-5492.
[] [PMID: 26566624]
Yang, K.; Xia, B.; Wang, W.; Cheng, J.; Yin, M.; Xie, H.; Li, J.; Ma, L.; Yang, C.; Li, A.; Fan, X.; Dhillon, H.S.; Hou, Y.; Lou, G.; Li, K. A comprehensive analysis of metabolomics and transcriptomics in cervical cancer. Sci. Rep., 2017, 7, 43353.
[] [PMID: 28225065]
Ye, N.; Liu, C.; Shi, P. Metabolomics analysis of cervical cancer, cervical intraepithelial neoplasia and chronic cervicitis by 1H NMR spectroscopy. Eur. J. Gynaecol. Oncol., 2015, 36(2), 174-180.
[PMID: 26050356]
Hasim, A.; Ali, M.; Mamtimin, B.; Ma, J.Q.; Li, Q.Z.; Abudula, A. Metabonomic signature analysis of cervical carcinoma and precancerous lesions in women by (1)H NMR spectroscopy. Exp. Ther. Med., 2012, 3(6), 945-951.
[] [PMID: 22969997]
Muñoz, N.; Hernandez-Suarez, G.; Méndez, F.; Molano, M.; Posso, H.; Moreno, V.; Murillo, R.; Ronderos, M.; Meijer, C.; Muñoz, A. Instituto Nacional de Cancerología HPV Study Group. Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women. Br. J. Cancer, 2009, 100(7), 1184-1190.
[] [PMID: 19293802]
Walker, H.; Burrell, M.; Flatley, J.; Powers, H. A metabolite profiling method for diagnosis of precancerous cervical lesions and HPV persistence. Bioanalysis, 2017, 9(8), 601-608.
[] [PMID: 28508693]
Hou, Y.; Yin, M.; Sun, F.; Zhang, T.; Zhou, X.; Li, H.; Zheng, J.; Chen, X.; Li, C.; Ning, X.; Lou, G.; Li, K. A metabolomics approach for predicting the response to neoadjuvant chemotherapy in cervical cancer patients. Mol. Biosyst., 2014, 10(8), 2126-2133.
[] [PMID: 24865370]
Chai, Y.; Wang, J.; Wang, T.; Yang, Y.; Su, J.; Shi, F.; Wang, J.; Zhou, X.; He, B.; Ma, H.; Liu, Z. Application of 1H NMR spectroscopy-based metabonomics to feces of cervical cancer patients with radiation-induced acute intestinal symptoms. Radiother. Oncol., 2015, 117(2), 294-301.
[] [PMID: 26277430]
Liang, Q.; Yu, Q.; Wu, H.; Zhu, Y-Z.; Zhang, A-H. Metabolite fingerprint analysis of cervical cancer using LC-QTOF/MS and multivariate data analysis. Anal. Methods, 2014, 6(12), 3937-3942.
Fan, L.; Zhang, W.; Yin, M.; Zhang, T.; Wu, X.; Zhang, H.; Sun, M.; Li, Z.; Hou, Y.; Zhou, X.; Lou, G.; Li, K. Identification of metabolic biomarkers to diagnose epithelial ovarian cancer using a UPLC/QTOF/MS platform. Acta Oncol., 2012, 51(4), 473-479.
[] [PMID: 22283470]
Lee, J.H.; Kim, Y.H.; Kim, K-H.; Cho, J.Y.; Woo, S.M.; Yoo, B.C.; Kim, S.C. Profiling of serum metabolites using MALDI-TOF and Triple-TOF mass spectrometry to develop a screen for ovarian cancer. Cancer Res. Treat., 2018, 50(3), 883-893.
[] [PMID: 28934848]
Slupsky, C.M.; Steed, H.; Wells, T.H.; Dabbs, K.; Schepansky, A.; Capstick, V.; Faught, W.; Sawyer, M.B. Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers. Clin. Cancer Res., 2010, 16(23), 5835-5841.
[] [PMID: 20956617]
Zhang, T.; Wu, X.; Ke, C.; Yin, M.; Li, Z.; Fan, L.; Zhang, W.; Zhang, H.; Zhao, F.; Zhou, X.; Lou, G.; Li, K. Identification of potential biomarkers for ovarian cancer by urinary metabolomic profiling. J. Proteome Res., 2013, 12(1), 505-512.
[] [PMID: 23163809]
Corrado, G.; Salutari, V.; Palluzzi, E.; Distefano, M.G.; Scambia, G.; Ferrandina, G. Optimizing treatment in recurrent epithelial ovarian cancer. Expert Rev. Anticancer Ther., 2017, 17(12), 1147-1158.
[] [PMID: 29086618]
Turkoglu, O.; Zeb, A.; Graham, S.; Szyperski, T.; Szender, J.B.; Odunsi, K.; Bahado-Singh, R. Metabolomics of biomarker discovery in ovarian cancer: a systematic review of the current literature. Metabolomics, 2016, 12(4), 60.
[] [PMID: 28819352]
Fan, L.; Yin, M.; Ke, C.; Ge, T.; Zhang, G.; Zhang, W.; Zhou, X.; Lou, G.; Li, K. Use of plasma metabolomics to identify diagnostic biomarkers for early stage epithelial ovarian cancer. J. Cancer, 2016, 7(10), 1265-1272.
[] [PMID: 27390602]
Xie, H.; Hou, Y.; Cheng, J.; Openkova, M.S.; Xia, B.; Wang, W.; Li, A.; Yang, K.; Li, J.; Xu, H.; Yang, C.; Ma, L.; Li, Z.; Fan, X.; Li, K.; Lou, G. Metabolic profiling and novel plasma biomarkers for predicting survival in epithelial ovarian cancer. Oncotarget, 2017, 8(19), 32134-32146.
[] [PMID: 28389631]
Zhang, H.; Ge, T.; Cui, X.; Hou, Y.; Ke, C.; Yang, M.; Yang, K.; Wang, J.; Guo, B.; Zhang, F.; Lou, G.; Li, K. Prediction of advanced ovarian cancer recurrence by plasma metabolic profiling. Mol. Biosyst., 2015, 11(2), 516-521.
[] [PMID: 25424060]
Garcia, E.; Andrews, C.; Hua, J.; Kim, H.L.; Sukumaran, D.K.; Szyperski, T.; Odunsi, K. Diagnosis of early stage ovarian cancer by 1H NMR metabonomics of serum explored by use of a microflow NMR probe. J. Proteome Res., 2011, 10(4), 1765-1771.
[] [PMID: 21218854]
Hilvo, M.; de Santiago, I.; Gopalacharyulu, P.; Schmitt, W.D.; Budczies, J.; Kuhberg, M.; Dietel, M.; Aittokallio, T.; Markowetz, F.; Denkert, C.; Sehouli, J.; Frezza, C.; Darb-Esfahani, S.; Braicu, E.I. Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of ovarian high-grade serous carcinomas. Cancer Res., 2016, 76(4), 796-804.
[] [PMID: 26685161]
Ke, C.; Hou, Y.; Zhang, H.; Fan, L.; Ge, T.; Guo, B.; Zhang, F.; Yang, K.; Wang, J.; Lou, G.; Li, K. Large-scale profiling of metabolic dysregulation in ovarian cancer. Int. J. Cancer, 2015, 136(3), 516-526.
[] [PMID: 24895217]
Selen, E.S.; Bolandnazar, Z.; Tonelli, M.; Bütz, D.E.; Haviland, J.A.; Porter, W.P.; Assadi-Porter, F.M. Assadi-Porter, F.M. NMR metabolomics show evidence for mitochondrial oxidative stress in a mouse model of polycystic ovary syndrome. J. Proteome Res., 2015, 14(8), 3284-3291.
[] [PMID: 26076986]
Tata, B.; Mimouni, N.E.H.; Barbotin, A-L.; Malone, S.A.; Loyens, A.; Pigny, P.; Dewailly, D.; Catteau-Jonard, S.; Sundström-Poromaa, I.; Piltonen, T.T.; Dal Bello, F.; Medana, C.; Prevot, V.; Clasadonte, J.; Giacobini, P. Elevated prenatal anti-Müllerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nat. Med., 2018, 24(6), 834-846.
[] [PMID: 29760445]
Balaban, B.; Urman, B. Effect of oocyte morphology on embryo development and implantation. Reprod. Biomed. Online, 2006, 12(5), 608-615.
[] [PMID: 16790106]
Arya, B.K.; Haq, A.U.; Chaudhury, K. Oocyte quality reflected by follicular fluid analysis in poly cystic ovary syndrome (PCOS): a hypothesis based on intermediates of energy metabolism. Med. Hypotheses, 2012, 78(4), 475-478.
[] [PMID: 22336088]
Galazis, N.; Iacovou, C.; Haoula, Z.; Atiomo, W. Metabolomic biomarkers of impaired glucose tolerance and type 2 diabetes mellitus with a potential for risk stratification in women with polycystic ovary syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol., 2012, 160(2), 121-130.
[] [PMID: 22136882]
Zhao, Y.; Fu, L.; Li, R.; Wang, L.N.; Yang, Y.; Liu, N.N.; Zhang, C.M.; Wang, Y.; Liu, P.; Tu, B.B.; Zhang, X.; Qiao, J. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis. BMC Med., 2012, 10, 153.
[] [PMID: 23198915]
Sun, L.; Hu, W.; Liu, Q.; Hao, Q.; Sun, B.; Zhang, Q.; Mao, S.; Qiao, J.; Yan, X. Metabonomics reveals plasma metabolic changes and inflammatory marker in polycystic ovary syndrome patients. J. Proteome Res., 2012, 11(5), 2937-2946.
[] [PMID: 22428626]
Atiomo, W.; Daykin, C.A. Metabolomic biomarkers in women with polycystic ovary syndrome: a pilot study. Mol. Hum. Reprod., 2012, 18(11), 546-553.
[] [PMID: 22809877]
Zhao, X.; Xu, F.; Qi, B.; Hao, S.; Li, Y.; Li, Y.; Zou, L.; Lu, C.; Xu, G.; Hou, L. Serum metabolomics study of polycystic ovary syndrome based on liquid chromatography-mass spectrometry. J. Proteome Res., 2014, 13(2), 1101-1111.
[] [PMID: 24428203]
Dong, F.; Deng, D.; Chen, H.; Cheng, W.; Li, Q.; Luo, R.; Ding, S. Serum metabolomics study of polycystic ovary syndrome based on UPLC-QTOF-MS coupled with a pattern recognition approach. Anal. Bioanal. Chem., 2015, 407(16), 4683-4695.
[] [PMID: 25860656]
Wang, W.; Wang, S.; Tan, S.; Wen, M.; Qian, Y.; Zeng, X.; Guo, Y.; Yu, C. Detection of urine metabolites in polycystic ovary syndrome by UPLC triple-TOF-MS. Clin. Chim. Acta, 2015, 448, 39-47.
[] [PMID: 26093338]
Chen, Y.X.; Zhang, X.J.; Huang, J.; Zhou, S.J.; Liu, F.; Jiang, L.L.; Chen, M.; Wan, J.B.; Yang, D.Z. UHPLC/Q-TOFMS-based plasma metabolomics of polycystic ovary syndrome patients with and without insulin resistance. J. Pharm. Biomed. Anal., 2016, 121, 141-150.
[] [PMID: 26808063]
RoyChoudhury, S.; Mishra, B.P.; Khan, T.; Chattopadhayay, R.; Lodh, I.; Datta Ray, C.; Bose, G.; Sarkar, H.S.; Srivastava, S.; Joshi, M.V.; Chakravarty, B.; Chaudhury, K. Serum metabolomics of Indian women with polycystic ovary syndrome using 1H NMR coupled with a pattern recognition approach. Mol. Biosyst., 2016, 12(11), 3407-3416.
[] [PMID: 27714060]
Chang, A.Y.; Lalia, A.Z.; Jenkins, G.D.; Dutta, T.; Carter, R.E.; Singh, R.J.; Nair, K.S. Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome. Metabolism, 2017, 71, 52-63.
[] [PMID: 28521878]
Szczuko, M.; Zapałowska-Chwyć, M.; Drozd, A.; Maciejewska, D.; Starczewski, A.; Stachowska, E. Metabolic pathways of oleic and palmitic acid are intensified in PCOS patients with normal androgen levels. Prostaglandins Leukot. Essent. Fatty Acids, 2017, 126, 105-111.
[] [PMID: 29031387]
RoyChoudhury. S.; More, T.H.; Chattopadhyay, R Lodh, I.; Ray, C.D.; Bose, G.; Sarkar, H.S.; Chakravarty, B.; Rapole, S.; Chaudhury, K. Polycystic ovary syndrome in Indian women: a mass spectrometry based serum metabolomics approach. Metabolomics, 2017, 13(10), 115.
Insenser, M.; Montes-Nieto, R.; Murri, M.; Escobar-Morreale, H.F. Proteomic and metabolomic approaches to the study of polycystic ovary syndrome. Mol. Cell. Endocrinol., 2013, 370(1-2), 65-77.
[] [PMID: 23422073]
Murri, M.; Insenser, M.; Escobar-Morreale, H.F. Metabolomics in polycystic ovary syndrome. Clin. Chim. Acta, 2014, 429, 181-188.
[] [PMID: 24368231]
Medicine, P.C.A.S.R. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil. Steril., 2012, 98(3), 591-598.
[] [PMID: 22704630]
Meuleman, C.; Vandenabeele, B.; Fieuws, S.; Spiessens, C.; Timmerman, D.; D’Hooghe, T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil. Steril., 2009, 92(1), 68-74.
[] [PMID: 18684448]
Scutiero, G.; Iannone, P.; Bernardi, G.; Bonaccorsi, G.; Spadaro, S.; Volta, C.A.; Greco, P.; Nappi, L. Oxidative stress and endometriosis: a systematic review of the literature. Oxid. Med. Cell. Longev., 2017, 2017 7265238
[] [PMID: 29057034]
Vouk, K.; Hevir, N.; Ribić-Pucelj, M.; Haarpaintner, G.; Scherb, H.; Osredkar, J.; Möller, G.; Prehn, C.; Rižner, T.L.; Adamski, J. Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis. Hum. Reprod., 2012, 27(10), 2955-2965.
[] [PMID: 22859507]
Yang, H.; Lau, W.B.; Lau, B.; Xuan, Y.; Zhou, S.; Zhao, L.; Luo, Z.; Lin, Q.; Ren, N.; Zhao, X.; Wei, Y. A mass spectrometric insight into the origins of benign gynecological disorders. Mass Spectrom. Rev., 2017, 36(3), 450-470.
[] [PMID: 26633258]
Somigliana, E.; Vercellini, P.; Vigano’, P.; Benaglia, L.; Crosignani, P.G.; Fedele, L. Non-invasive diagnosis of endometriosis: the goal or own goal? Hum. Reprod., 2010, 25(8), 1863-1868.
[] [PMID: 20519246]
Mol, B.W.; Bayram, N.; Lijmer, J.G.; Wiegerinck, M.A.; Bongers, M.Y.; van der Veen, F.; Bossuyt, P.M. The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis. Fertil. Steril., 1998, 70(6), 1101-1108.
[] [PMID: 9848302]
McLeod, B.S.; Retzloff, M.G. Epidemiology of endometriosis: an assessment of risk factors. Clin. Obstet. Gynecol., 2010, 53(2), 389-396.
[] [PMID: 20436315]
Draj, H.A.; Abbas, A.A.; Abdullah, T.H. Serum levels of glycodelin a and soluble intracellular adhesion molecule-1 as biomarkers for endometriosis. Iraqi JMS, 2017, 15(4), 345-349.
Ekarattanawong, S.; Tanprasertkul, C.; Somprasit, C.; Chamod, P.; Tiengtip, R.; Bhamarapravatana, K.; Suwannarurk, K. Possibility of using superoxide dismutase and glutathione peroxidase as endometriosis biomarkers. Int. J. Womens Health, 2017, 9, 711-716.
[] [PMID: 29026339]
Reis, F.M.; Monteiro, C.S.; Carneiro, M.M. Biomarkers of pelvic endometriosis. Rev. Bras. Ginecol. Obstet., 2017, 39(3), 91-93.
[] [PMID: 28359109]
Trapero, C.; Jover, L.; Fernández-Montolí, M.E.; García-Tejedor, A.; Vidal, A.; Gómez de Aranda, I.; Ponce, J.; Matias-Guiu, X.; Martín-Satué, M. Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of ovarian endometriomas as candidate biomarkers of endometriosis. Am. J. Reprod. Immunol., 2018, 79(2)
[] [PMID: 29194839]
Dutta, M.; Joshi, M.; Srivastava, S.; Lodh, I.; Chakravarty, B.; Chaudhury, K. A metabonomics approach as a means for identification of potential biomarkers for early diagnosis of endometriosis. Mol. Biosyst., 2012, 8(12), 3281-3287.
[] [PMID: 23079773]
Vissers, Y.L.; Dejong, C.H.; Luiking, Y.C.; Fearon, K.C.; von Meyenfeldt, M.F.; Deutz, N.E. Plasma arginine concentrations are reduced in cancer patients: evidence for arginine deficiency? Am. J. Clin. Nutr., 2005, 81(5), 1142-1146.
[] [PMID: 15883440]
Vodolazkaia, A.; El-Aalamat, Y.; Popovic, D.; Mihalyi, A.; Bossuyt, X.; Kyama, C.M.; Fassbender, A.; Bokor, A.; Schols, D.; Huskens, D.; Meuleman, C.; Peeraer, K.; Tomassetti, C.; Gevaert, O.; Waelkens, E.; Kasran, A.; De Moor, B.; D’Hooghe, T.M. Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. Hum. Reprod., 2012, 27(9), 2698-2711.
[] [PMID: 22736326]
Ghazi, N.; Arjmand, M.; Akbari, Z.; Mellati, A.O.; Saheb-Kashaf, H.; Zamani, Z. (1)H NMR- based metabolomics approaches as non- invasive tools for diagnosis of endometriosis. Int. J. Reprod. Biomed. (Yazd), 2016, 14(1), 1-8.
[] [PMID: 27141542]
Jadoul, P.; Kitajima, M.; Donnez, O.; Squifflet, J.; Donnez, J. Surgical treatment of ovarian endometriomas: state of the art? Fertil. Steril., 2012, 98(3), 556-563.
[] [PMID: 22763094]
Kouremenos, K.A.; Johansson, M.; Marriott, P.J. Advances in gas chromatographic methods for the identification of biomarkers in cancer. J. Cancer, 2012, 3, 404-420.
[] [PMID: 23074381]
Spratlin, J.L.; Serkova, N.J.; Eckhardt, S.G. Clinical applications of metabolomics in oncology: a review. Clin. Cancer Res., 2009, 15(2), 431-440.
[] [PMID: 19147747]
Cuvillier, O. Sphingosine in apoptosis signaling. Biochim. Biophys. Acta, 2002, 1585(2-3), 153-162.
[] [PMID: 12531549]
Sano, M.; Morishita, T.; Nozaki, M.; Yokoyama, M.; Watanabe, Y.; Nakano, H. Elevation of the phospholipase A2 activity in peritoneal fluid cells from women with endometriosis. Fertil. Steril., 1994, 61(4), 657-662.
[] [PMID: 8150107]
Vouk, K.; Ribič-Pucelj, M.; Adamski, J.; Rižner, T.L. Altered levels of acylcarnitines, phosphatidylcholines, and sphingomyelins in peritoneal fluid from ovarian endometriosis patients. J. Steroid Biochem. Mol. Biol., 2016, 159, 60-69.
[] [PMID: 26921767]
Letsiou, S.; Peterse, D.P.; Fassbender, A.; Hendriks, M.M.; van den Broek, N.J.; Berger, R.; O, D.F.; Vanhie, A.; Vodolazkaia, A.; Van Langendonckt, A.; Donnez, J.; Harms, A.C.; Vreeken, R.J.; Groothuis, P.G.; Dolmans, M.M.; Brenkman, A.B.; D’Hooghe, T.M. Endometriosis is associated with aberrant metabolite profiles in plasma. Fertil. Steril., 2017, 107(3), 699-706.e6.
[] [PMID: 28259259]
Melo, A.S.; Rosa-e-Silva, J.C.; Rosa-e-Silva, A.C.; Poli-Neto, O.B.; Ferriani, R.A.; Vieira, C.S. Unfavorable lipid profile in women with endometriosis. Fertil. Steril., 2010, 93(7), 2433-2436.
[] [PMID: 19969295]
Marianna, S.; Alessia, P.; Susan, C.; Francesca, C.; Angela, S.; Francesca, C.; Antonella, N.; Patrizia, I.; Nicola, C.; Emilio, C. Metabolomic profiling and biochemical evaluation of the follicular fluid of endometriosis patients. Mol. Biosyst., 2017, 13(6), 1213-1222.
[] [PMID: 28475193]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy