The significance of lipidomic changes in ovarian neoplasms

Iurova M.V., Pavlovich S.V., Khabas G.N., Chagovets V.V., Frankevich V.E., Ashrafyan L.A.

1) Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia; 2) I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia
A number of lipids have tumor-initiating activity and this is the reason why the term "oncolipid" has been introduced. The content of various oncolipids in the tumor microenvironment reflects their ability to initiate and maintain the stages of carcinogenesis. This review analyzes the data available in the 2016–2020 literature from the databases Scopus, Medline, Cochrane, PubMed, eLibrary (with access to a full-text resource), and Web of Science, which is devoted to the study of lipid metabolic processes in ovarian malignancies. It analyzes the current promising studies of oncolipidomics, presents the possibilities of detecting early stage disease, summarizes data on the involvement of lipids in the process of initiation and progression of serous ovarian cancer and on the diagnostic and prognostic value of detecting lipidomic changes by mass spectrometry, and traces the relationship of these changes to the aggressiveness of the disease and its sensitivity to chemotherapy. The changes in the lipid composition are the pathogenetic result of accelerated cell division, impaired activation of the inositol-3-phosphate pathway, and intensive fatty acid β-oxidation. The largest number of studies is devoted to the classes of lipids, such as phosphatidylcholines and sphingomyelins. The activity of lysophosphatidic acid is one of the key factors in the process of tumor progression in ovarian cancer.
Conclusion. Interpretation of the study results is possible due to the unified lipid classification available in the Lipid Maps and Human Metabolome Database.


mass spectrometry
molecular biology
ovarian cancer


  1. Amoroso M.R., Matassa D.S., Agliarulo I., Avolio R., Maddalena F., Condelli V. et al. Stress-adaptive response in ovarian cancer drug resistance: role of TRAP1 in oxidative metabolism-driven inflammation. Adv. Protein Chem. Struct. Biol. 2017; 108: 163-98.
  2. Каприн А.Д., Старинский В.В., Шахзадова А.О., ред. Состояние онкологической помощи населению России в 2019 году. М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2020. 239с. [Kaprin A.D., Starinskiy V.V. The state of cancer care for the population of Russia in 2019. M., 2020. 239 p. (in Russian)].
  3. Ueland F.R., Li A.J. Serum biomarkers for evaluation of an adnexal mass for epithelial carcinoma of the ovary, fallopian tube, or peritoneum. UpToDate. 2016: 1-13.
  4. Tomao F., Di Pinto A., Sassu C.M., Bardhi E., Di Donato V., Muzii L. et al. Fertility preservation in ovarian tumours. Ecancermedicalscience. 2018; 12: 885.
  5. Ashraf M.A., Dasari P. Outcome of fertility-preserving surgery for ovarian malignancy in young women. Case Rep. 2018; 1(1): 51-4.
  6. Назаренко Т.А., Ашрафян Л.А., Джанашвили Л.Г., Мартиросян Я.О. Сохранение репродуктивного материала у онкологических больных как медико-социальная и организационная проблема. Онкология. Журнал им. П.А. Герцена. 2020; 9(1): 60-5. [Nazarenko T.A., Ashrafian L.A., Dzhanashvili L.G., Martirosyan Y.O. Retention of reproductive material in cancer patients as a sociomedical and organizational problem. P.A. Herzen Journal of Oncology. 2020; 9(1): 60-5. (in Russian)].
  7. Li J., Xie H., Li A., Cheng J., Yang K., Wang J. et al. Distinct plasma lipids profiles of recurrent ovarian cancer by liquid chromatography-mass spectrometry. Oncotarget. 2017; 8(29): 46834-45.
  8. Grossman D.C., Curry S.J., Owens D.K., Barry M.J., Davidson K.W., Doubeni C.A. et al. Screening for ovarian cancer US preventive services task force recommendation statement. JAMA. 2018; 319(6): 588-94.
  9. Swiatly A., Plewa S., Matysiak J., Kokot Z.J. Mass spectrometry-based proteomics techniques and their application in ovarian cancer research. J. Ovarian Res. 2018; 11(1): 88.
  10. Urban R.R., Pappas T.C., Bullock R.G., Munroe D.G., Bonato V., Agnew K., Goff B.A. Combined symptom index and second-generation multivariate biomarker test for prediction of ovarian cancer in patients with an adnexal mass. Gynecol. Oncol. 2018; 150(2): 318-23.
  11. Sans M., Gharpure K., Tibshirani R., Zhang J., Liang L., Liu J. et al. Metabolic markers and statistical prediction of serous ovarian cancer aggressiveness by ambient ionization mass spectrometry imaging. Cancer Res. 2017; 77(11): 2903-13.
  12. Торгомян Т.Р., Лазян М.П., Давтян А.Г., Батикян Т.Б., Казарян Р.А., Алексанян К.А., Галстян Г.М., Батикян Т.Б. Жирнокислотная модификация липидов в мононуклеарных клетках крови при раке молочной железы и яичников. Биологический журнал Армении. 2012; 64(2): 73-9. [Torgomyan T.R., Lazyan M.P., Davtyan A.G. et al. Fatty acid modification of lipids in blood mononuclear cells in breast and ovarian cancer. 2012; 2(64): 73-9. (in Russian)].
  13. Xu Y. Lysophospholipid signaling in the epithelial ovarian cancer tumor microenvironment. Cancers (Basel). 2018; 10(7): 277.
  14. Guo Y., Ren J., Li X., Liu X., Liu N., Wang Y., Li Z. Simultaneous quantification of serum Multi-Phospholipids as potential biomarkers for differentiating different pathophysiological states of lung, stomach, intestine, and pancreas. J. Cancer. 2017; 8(12): 2191-204.
  15. Wolrab D., Robert Jirasko R., Michaela Chocholouskova M., Peterka O., Holcapek M. Oncolipidomics: mass spectrometric quantitation of lipids in cancer research. Trends Anal. Chem. 2019; 120: 115480.
  16. Ray U., Roy Chowdhury S., Vasudevan M., Bankar K., Roychoudhury S., Roy S.S. Gene regulatory networking reveals the molecular cue to lysophosphatidic acid-induced metabolic adaptations in ovarian cancer cells. Mol. Oncol. 2017; 11(5): 491-516.
  17. Sud M., Fahy E., Cotter D., Brown A., Dennis E.A., Glass C.K. et al. LMSD: LIPID MAPS structure database. Nucleic Acids Res. 2007; 35(Database issue): D527-32.
  18. Hannun Y.A., Obeid L.M. Sphingolipids and their metabolism in physiology and disease. Nat. Rev. Mol. Cell Biol. 2018; 19(3): 175-91.
  19. Hajj C., Becker-Flegler K.A., Haimovitz-Friedman A. Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways. Biol. Chem. 2015; 396(6-7): 669-79.
  20. Espaillat M.P., Shamseddine A., Adada M., Hannun Y., Obeid L. Ceramide and sphingosine-1-phosphate in cancer, two faces of the sphinx. Transl. Cancer Res. 2015; 4(5): 484-99.
  21. Islam S.R., Manna S.K. Lipidomic analysis of cancer cell and tumor tissues. In: Haznadar M., ed. Cancer metabolism. Methods in molecular biology. New York, NY: Humana Press; 2019: 175-204.
  22. Токарева А.О., Чаговец В.В., Родионов В.В., Кометова В.В., Родионова М.В., Стародубцева Н.Л., Франкевич В.Е. Липидные маркеры метастатического поражения регионарных лимфоузлов у больных раком молочной железы. Акушерство и гинекология. 2020; 8: 133-40. [Tokareva A.O., Chagovets V.V., Rodionov V.V., Kometova V.V., Rodionova M.V., Starodubtseva N.L., Frankevich V.E. Lipid markers of metastatic lesions in regional lymph nodes in patients with breast cancer. Akusherstvo i Ginekologiya/ Obstetrics and gynecology. 2020; 8: 133-40. (in Russian)].
  23. Denkert C., Budczies J., Kind T., Weichert W., Tablack P., Sehouli J. et al. Mass spectrometry-based metabolic profiling reveals different metabolite patterns in invasive ovarian carcinomas and ovarian borderline tumors. Cancer Res. 2006; 66(22): 10795-804.
  24. Cuello M.A., Kato S., Liberona F. The impact on high-grade serous ovarian cancer of obesity and lipid metabolism-related gene expression patterns: the underestimated driving force affecting prognosis. J. Cell. Mol. Med. 2018; 22(3):1805-15.
  25. Pagès C., Simon M.F., Valet P., Saulnier-Blache J.S. Lysophosphatidic acid synthesis and release. Prostaglandins Other Lipid Mediat. 2001; 64(1-4): 1-10.
  26. Hiramatsu K., Serada S., Enomoto T., Takahashi Y., Nakagawa S., Nojima S. et al. LSR antibody therapy inhibits ovarian epithelial tumor growth by inhibiting lipid uptake. Cancer Res. 2018; 78(2): 516-27.
  27. Hilvo M., de Santiago I., Gopalacharyulu P., Schmitt W.D., Budczies J., Kuhberg M. et al. Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of ovarian high-grade serous carcinomas. Cancer Res. 2016; 76(4): 796-804.
  28. Niemi R.J., Braicu E.I., Kulbe H., Koistinen K.M., Sehouli J., Puistola U. et al. Ovarian tumours of different histologic type and clinical stage induce similar changes in lipid metabolism. Br. J. Cancer. 2018; 119(7): 847-54.
  29. Braicu E.I., Darb-Esfahani S., Schmitt W.D., Koistinen K.M., Heiskanen L., Pöhö P. et al. High-grade ovarian serous carcinoma patients exhibit profound alterations in lipid metabolism. Oncotarget. 2017; 8(61): 102912-22.
  30. Ghahremanfard F., Mirmohammadkhani M., Shahnazari B., Gholami G., Mehdizadeh J. The valuable role of measuring serum lipid profile in cancer progression. Oman Med. J. 2015; 30(5): 353-7.
  31. Ke C., Hou Y., Zhang H., Fan L., Ge T., Guo B. et al. Large-scale profiling of metabolic dysregulation in ovarian cancer. Int. J. Cancer. 2015; 136(3): 516-26.
  32. Rahmioglu N., Fassbender A., Vitonis A.F., Tworoger S.S., Hummelshoj L., D'Hooghe T.M. et al. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research. Fertil. Steril. 2014; 102(5): 1233-43.
  33. Gaul D.A., Mezencev R., Long T.Q., Jones C.M., Benigno B.B., Gray A. et al. Highly-accurate metabolomic detection of early-stage ovarian cancer. Sci. Rep. 2015; 5: 16351.
  34. Buas M.F., Gu H., Djukovic D., Zhu J., Drescher C.W., Urban N. et al. Identification of novel candidate plasma metabolite biomarkers for distinguishing serous ovarian carcinoma and benign serous ovarian tumors. Gynecol. Oncol. 2016; 140(1): 138-44.
  35. Hou Y., Li J., Xie H., Sun F., Yang K., Wang J. et al. Differential plasma lipids profiling and lipid signatures as biomarkers in the early diagnosis of ovarian carcinoma using UPLC-MS. Metabolomics. 2016; 12(2): Article 18.
  36. Knapp P., Bodnar L., Błachnio-Zabielska A., Świderska M., Chabowski A. Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer. Gynecol. Oncol. 2017; 147(1): 139-44.
  37. Jones C.M., Monge M.E., Kim J., Matzuk M.M., Fernández F.M. Metabolomic serum profiling detects early-stage high-grade serous ovarian cancer in a mouse model. J. Proteome Res. 2015; 14(2): 917-27.
  38. Yan F., Zhao H., Zeng Y. Lipidomics : a promising cancer biomarker. Clin. Transl. Med. 2018; 7(1): 21.
  39. Liu J., Liu X., Xiao Z., Locasale J.W. Quantitative evaluation of a high resolution lipidomics platform. Posted May 04, 2019.
  40. Wefers C., Duiveman-de Boer T., Zusterzeel P.L.M., Massuger L.F.A.G., Fuchs D., Torensma R. et al. Different lipid regulation in ovarian cancer: Inhibition of the immune system. Int. J. Mol. Sci. 2018; 19(1): 273.
  41. Xu Y., Shen Z., Wiper D.W., Wu M., Morton R.E., Elson P. et al. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA. 1998; 280(8): 719-23.
  42. Delcourt V., Franck J., Leblanc E., Narducci F., Robin Y.M., Gimeno J.P. et al. Combined mass spectrometry imaging and top-down microproteomics reveals evidence of a hidden proteome in ovarian cancer. EBioMedicine. 2017; 21: 55-64.
  43. Migda M., Bartosz M., Migda M.S., Kierszk M., Katarzyna G., Maleńczyk M. Diagnostic value of the gynecology imaging reporting and data system (GI-RADS) with the ovarian malignancy marker CA-125 in preoperative adnexal tumor assessment. J. Ovarian Res. 2018; 11(1): 92.
  44. Qin W., Xiong Y., Chen J., Huang Y., Liu T. DC-CIK cells derived from ovarian cancer patient menstrual blood activate the TNFR1-ASK1-AIP1 pathway to kill autologous ovarian cancer stem cells. J. Cell. Mol. Med. 2018; 22(7): 3364-76.
  45. Liu X.H., Man Y.N., Wu X.Z. Recurrence season impacts the survival of epithelial ovarian cancer patients. Asian Pacific J. Cancer Prev. 2014; 15(4): 1627-32.
  46. Wahner Hendrickson A.E., Hawthorne K.M., Goode E.L., Kalli K.R., Goergen K.M., Bakkum-Gamez J.N. et al. Assessment of published models and prognostic variables in epithelial ovarian cancer at Mayo Clinic. Gynecol. Oncol. 2015; 137(1): 77-85.
  47. Payne A.W., Pant D.K., Pan T.C., Chodosh L.A. Ceramide kinase promotes tumor cell survival and mammary tumor recurrence. Cancer Res. 2014; 74(21): 6352-63.
  48. Jolanta B., Joanna B., Diana H.Z., Krystyna S. Composition and concentration of serum fatty acids of phospholipids depend on tumour location and disease progression in colorectal patients. J. Med. Biochem. 2018; 37(1): 39-45.
  49. Yan G., Li L., Zhu B., Li Y. Lipidome in colorectal cancer. Oncotarget. 2016; 7(22): 33429-39.
  50. Du Y., Wang Q., Zhang X., Wang X., Qin C., Sheng Z. et al. Lysophosphatidylcholine acyltransferase 1 upregulation and concomitant phospholipid alterations in clear cell renal cell carcinoma. J. Exp. Clin. Cancer Res. 2017; 36(1): 66.
  51. Sherubin E.J., Kannan K.S., Kumar D.N., Joseph I. Estimation of plasma lipids and its significance on histopathological grades in oral cancer: Prognostic significance an original research. J. Oral Maxillofac. Pathol. 2013; 17(1): 4-9.
  52. Vinayavekhin N., Sueajai J., Chaihad N., Panrak R., Chokchaisiri R., Sangvanich P. et al. Serum lipidomics analysis of ovariectomized rats under Curcuma comosa treatment. J. Ethnopharmacol. 2016; 192: 273-82.
  53. Perween R., Khan T. Borderline ovarian tumor. An overview and evidence based management. Pan. Asian J. Obs. Gyn. 2019; 2(1): 30-6.

Received 28.01.2021

Accepted 17.06.2021

About the Authors

Mariia V. Iurova, MD, specialist, Department of System Biology in Reproduction, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; post-graduate student, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Department of Obstetrics, Gynecology, Perinatology and Reproductive Health; the Faculty of Higher Professional Training. Tel.: +7(495)438-20-88. E-mail: ORCID: 0000-0002-0179-7635. 117997, Russia, Moscow, Ac. Oparina str., 4.
Stanislav V. Pavlovich, obstetrician-gynecologist, MD, PhD, Scientific secretary, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University). Tel.: +7(495)438-20-88. E-mail: ORCID: 0000-0002-1313-7079. 117997, Russia, Moscow, Ac. Oparina str., 4.
Grigory N. Khabas, surgeon, oncologist, obstetrician-gynecologist, MD, PhD, Head of the Department of Innovative Oncology and Gynecology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. Tel.: +7(495)438-78-33. E-mail:
117997, Russia, Moscow, Ac. Oparina str., 4.
Vitaliy V. Chagovets, PhD, Senior Researcher of the Laboratory of Proteomics and Metabolomics in Human Reproduction, Department of Systems Biology,
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. Tel.: +7(926)562-65-90.
E-mail: ORCID: 0000-0002-5120-376X. 117997, Russia, Moscow, Ac. Oparina str., 4.
Vladimir E. Frankevich, PhD, Head of the Department of System Biology in Reproduction, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. Tel.: +7(495)438-07-88 (ex. 2198). E-mail: ORCID: 0000-0002-9780-4579.
117997, Russia, Moscow, Ac. Oparina str., 4.
Lev A. Ashrafyan, Academician of the Russian Academy of Sciences, MD, Professor, Head of the Institute of Oncogynecology and Mammology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia. Tel.: +7(499)120-60-77. E-mail:
ORCID: 0000-0001-6396-4948. 117997, Russia, Moscow, Ac. Oparina str., 4.

For citation: Iurova M.V., Pavlovich S.V., Khabas G.N., Chagovets V.V., Frankevich V.E., Ashrafyan L.A. The significance of lipidomic changes in ovarian neoplasms.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 8: 39-48 (in Russian)

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.