Differential diagnosis of early-stage ovarian cancer based on the bioinformatic analysis of the blood metabolome

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Abstract

The early diagnosis of ovarian cancer (OC) represents an important step in reducing the number of fatal outcomes associated with the disease. Timely treatment initiation, minimizing the risk of recurrence and side effects of therapy, largely depend on early diagnosis.

Objective: To create stable panels of blood metabolites for differentiating healthy patients, patients with early-stage high-grade OC from other ovarian tumors.

Materials and methods. A search for markers for clustering of blood samples obtained from patients with verified stage I–II high-grade OC (n=10) and other proliferative processes (cystadenoma (n=30), endometrioid cyst (n=56), teratoma (n=21), borderline tumor (n=28), low-grade OC (n=16), stage III–IV high-grade (n=49)) and control volunteers (n=19) was performed. The study was carried out at the V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Moscow, Russia. The data were analyzed using recursive variable removal from the support vector machine and other statistical tools. There was a search for markers of malignant neoplasms (MNPs), followed by the analysis of their involvement in metabolic pathways. Models based on neural networks were built.

Results: The panels of metabolite-markers of early stages of MNPs were identified. The overlap of the obtained panels with metabolic pathway databases was studied. Artificial neural network models were developed to differentiate blood samples from I–II stage OC from controls with sensitivity and specificity of 90% and 89%, and from I–II stage OC from other ovarian neoplasms with sensitivity and specificity of 80% and 71%, respectively.

Conclusion: The introduction of post-genomic research has the potential to increase the diagnostic value of the methods used to detect ovarian MNPs at an earlier stage and also to expand the available data on the processes of carcinogenesis in the ovaries.

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About the authors

Maria V. Iurova

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Author for correspondence.
Email: m_yurova@oparina4.ru
ORCID iD: 0000-0002-0179-7635

PhD, obstetrician-gynecologist, oncologist, Researcher at the Scientific Polyclinic Department

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Alisa O. Tokareva

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: alisa.tokareva@phystech.edu
ORCID iD: 0000-0001-5918-9045

PhD (Physico-Mathematical Sciences), Specialist at the Laboratory of Clinical Proteomics

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Vitaliy V. Chagovets

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: vvchagovets@gmail.com

PhD (Physico-Mathematical Sciences), Head of the Laboratory of Metabolomics and Bioinformatics

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Natalia L. Starodubtseva

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: n_starodubtseva@oparina4.ru
ORCID iD: 0000-0001-6650-5915

PhD (Bio), Head of the Laboratory of Clinical Proteomics

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Vladimir E. Frankevich

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: v_vfrankevich@oparina4.ru

Dr. Sci. (Physico-Mathematical Sciences), Deputy Director of the Institute of Translational Medicine

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

References

  1. Каприн А.Д., Старинский В.В., Шахзадова А.О., ред. Состояние онкологической помощи населению России в 2023 году. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России; 2024. 262 с. [Kaprin A.D., Starinsky V.V., Shakhzadova A.O., eds. State of oncological care for the population of Russia in 2023. Moscow: P.A. Herzen MSROI - branch of the FSBI "National Medical Research Center of Radiology" of the Ministry of Health of Russia; 2024. 262 p. (in Russian)].
  2. Brenner D.R., Weir H.K., Demers A.A., Ellison L.F., Louzado C., Shaw A. et al.; Canadian Cancer Statistics Advisory Committee. Projected estimates of cancer in Canada in 2020. CMAJ. 2020; 192(9): E199-E205. https://dx.doi.org/10.1503/cmaj.191292.
  3. Юрова М.В., Хабас Г.Н., Павлович С.В. Оценка результатов комбинированного лечения пациентов с диссеминированным раком яичников. Гинекология. 2022; 24(2): 132-9. [Iurova M.V., Khabas G.N., Pavlovich S.V. Evaluation of results of combined treatment in patients with disseminated ovarian cancer. Gynecology. 2022; 24(2): 132-9. (in Russian)]. https://dx.doi.org/10.26442/20795696.2022.2.201438.
  4. Voelker R. Ovarian cancer screening tests don’t pass muster. JAMA. 2016; 316(15): 1538. https://dx.doi.org/10.1001/jama.2016.14614.
  5. Павлович С.В., Юрова М.В., Мелкумян А.Г., Франкевич В.Е., Хабас Г.Н., Чаговец В.В. Биомаркеры при новообразованиях яичников: возможности, ограничения и перспективы применения у женщин репродуктивного возраста. Акушерство и гинекология. 2019; 11: 65-73. [Pavlovich S.V., Yurova M.V., Melkumyan A.G., Frankevich V.E., Chagovets V.V., Khabas G.N. Biomarkers in ovarian neoplasms: opportunities, limitations, and prospects for using in reproductive-aged women. Obstetrics and Gynecology. 2019; (11): 65-73. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.11.65-73.
  6. Сенча А.Н, Поморцев А.В., Костюков К.В., Федоткина Е.П. Ультразвуковая диагностика заболеваний органов малого таза. Избранные вопросы. М.: МЕДпресс-информ; 2023. 260 с. [Sencha A.N., Pomortsev A.V., Kostyukov K.V., Fedotkina E.P. Ultrasound diagnosis of pelvic diseases. Selected questions. Moscow: MEDpress-inform; 2023. 260 p. (in Russian)].
  7. Тюляндина А.С., Коломиец Л.А., Морхов К.Ю., Нечушкина В.М., Покатаев И.А., Румянцев А.А., Тюляндин С.А., Урманчеева А.Ф., Хохлова С.В. Практические рекомендации по лекарственному лечению рака яичников, первичного рака брюшины и рака маточных труб. Практические рекомендации RUSSO, часть 1. Злокачественные опухоли. 2023; 13(3s2-1): 201-15. [Tyulyandina A.S., Kolomiets L.A., Morkhov K.Yu., Nechushkina V.M., Pokataev I.A., Rumyantsev A.A., Tyulyandin S.A., Urmancheeva A.F., Khokhlova S.V. Practical guidelines for the drug treatment of ovarian cancer, primary peritoneal cancer and fallopian tube cancer. RUSSO Practical guidelines, part 1. Malignant Tumours. 2023; 13(3s2-1): 201-15. (in Russian)]. https://dx.doi.org/10.18027/2224-5057-2023-13-3s2-1-201-215.
  8. 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)]. https://dx.doi.org/10.17116/onkolog2020901160.
  9. Ashraf M.A., Dasari P. Outcome of fertility-preserving surgery for ovarian malignancy in young women. Case Rep. 2018; 1(1): 51-4.
  10. Чаговец В.В., Васильев В.Г., Юрова М.В., Хабас Г.Н., Павлович С.В., Стародубцева Н.Л., Майборода О.А. Метаболомная подпись свободных муцинов при онкологических заболеваниях: CA125 и рак яичников высокой степени злокачественности. Вестник РГМУ. 2021; 6: 10-5. [Chagovets V.V., Vasil’iev V.G., Iurova M.V., Khabas G.N., Pavlovich S.V., Starodubtseva N.L., Mayboroda O.A. Metabolic "footprints" of the circulating cancer mucins: CA125 in the high-grade ovarian cancer. Bulletin of RSMU. 2021; (6): 10-5. (in Russian)]. https://dx.doi.org/10.24075/vrgmu.2021.065.
  11. 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. https://dx.doi.org/10.1002/ijc.29010.

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2. Fig. 1. Volcano diagram of markers obtained using OPLS. A) To separate the control group and the group with tumor lesions of the ovary; Б) To separate the control group and the group with early stage OC. Blue indicates points for which the statistical significance of the coincidence of medians is less than 0.05; red - for which the statistical significance of the coincidence of medians is less than 0.05 and the ratio of medians is greater than 1.5

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3. Fig. 2. Volcano diagram of markers obtained using MOB-REP. A) To separate the control group and the group with any tumor lesion of the ovary (except for the early stage of ovarian cancer); Б) To separate the control group and the group with ovarian cancer at an early stage; В) to separate the group with early-stage ovarian cancer and the group with other tumor lesions of the ovary. Compounds for which the statistical significance of the median coincidence is greater than 0.05 and the median ratio is less than 1.5 are indicated in black, compounds for which the statistical significance of the median coincidence is less than 0.05 are indicated in blue, compounds for which the statistical significance of the median coincidence is less than 0.05 and the median ratio is greater than 1.5 are indicated in red.

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4. Fig. 3. A) Operating curves obtained from cross-validation of panel-based models generated using OPLS; Б) Operating curves obtained from cross-validation of panel-based models generated using MOB-REP. Black – classification “Healthy”/“ovarian lesions”, blue – classification “Healthy”/“OC stage I-II”, red – classification “ovarian lesions”/“OC stage I-II”

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