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

Iurova M.V., Tokareva A.O., Chagovets V.V., Starodubtseva N.L., Frankevich V.E.

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

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.  

Authors’ contributions: Iurova M.V. – developing the concept of the study, material collection, receiving funding, project management, verification, resource search, supervision, writing literature review, initial draft and editing; Tokareva A.O. – data curation, methodology, providing software, resource search, writing, editing; Chagovets V.V. – making formal analysis, methodology, providing software; Starodubtseva N.L. – methodology, making formal analysis, developing the concept of the study, supervising, writing, editing; Frankevich V.E. – making formal analysis, supervising, reviewing and editing.
Conflicts of interest: The authors declare that the study was conducted in the absence of any commercial or financial relationship that could be interpreted as a potential conflict of interest.
Funding: The study was carried out within the framework of the Russian Science Foundation Grant dated 29.12.2023 No. 24-25-00407 “New approaches of application of artificial intelligence capabilities to differential diagnosis of benign tumors and ovarian cancer on the basis of blood metabolome characteristics determined by physical methods”.
Ethical Approval: The study was approved by the Ethical Review Board of the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology Moscow, Russia (Protocol No. 10 dated December 05, 2019). The study was initiated after obtaining the approval of the mentioned committee and was carried out in accordance with the Russia’s Federal Law of 27 July 2006 No. 152-FZ on Personal Data (‘the Law on Personal Data’) , Federal Law of 21.11.2011 No. 323-FZ “On the basics of health protection of citizens in the Russian Federation”, the provisions of the Declaration of Helsinki with all subsequent additions and amendments regulating scientific research on biomaterials obtained from human subjects, as well as the International ethical guidelines for biomedical research involving human subjects of the Council for International Organizations of Medical Sciences (CIOMS).
Patients’ Consent for Publication: The patients signed informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Iurova M.V., Tokareva A.O., Chagovets V.V., Starodubtseva N.L., Frankevich V.E. Differential diagnosis of early-stage ovarian cancer based on the bioinformatic analysis of the blood metabolome.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (12): 118-126 (in Russian)
https://dx.doi.org/10.18565/aig.2024.283

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About the Authors

Maria V. Iurova, PhD, obstetrician-gynecologist, oncologist, Researcher at the Scientific Polyclinic Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, m_yurova@oparina4.ru, https://orcid.org/0000-0002-0179-7635
Alisa O. Tokareva, PhD (Physico-Mathematical Sciences), Specialist at the Laboratory of Clinical Proteomics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(495)531-44-44 (ext. 3113), alisa.tokareva@phystech.edu, https://orcid.org/0000-0001-5918-9045
Vitaliy V. Chagovets, PhD (Physico-Mathematical Sciences), Head of the Laboratory of Metabolomics and Bioinformatics, V.I. Kulakov NMRC for OG&P, Ministry of Health
of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(495)438-21-98, vvchagovets@gmail.com
Natalia L. Starodubtseva, PhD (Bio), Head of the Laboratory of Clinical Proteomics, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
117997, Russia, Moscow, Ac. Oparin str., 4, https://orcid.org/0000-0001-6650-5915
Vladimir E. Frankevich, Dr. Sci. (Physico-Mathematical Sciences), Deputy Director of the Institute of Translational Medicine, V.I. Kulakov NMRC for OG&P,
Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, v_frankevich@oparina4.ru
Corresponding author: Maria V. Iurova, m_yurova@oparina4.ru

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