The genes copy number variation features in blood plasma of uterine cancer patients and disease prognosis

Denis S. Kutilin; Кутилин Денис Сергеевич; E. M. Frantsiyants; Франциянц Е. М.; I. V. Neskubina; Нескубина И. В.; A. I. Shikhlyarova; Шихлярова А. И.; V. A. Bandovkina; Бандовкина В. А.; P. S. Kachesova; Качесова П. С.; N. D. Cheryarina; Черярина Н. Д.; I. A. Udalenkova; Удаленкова И. А.; A. P. Menshenina; Меньшенина А. П.; E. A. Ozerkova; Озеркова Е. А.; Yu. S. Shatova; Шатова Ю. С.; A. A. Ovsyannikova; Овсянникова А. А.

doi:10.17650/2313-805X-2026-13-3-8-19

The genes copy number variation features in blood plasma of uterine cancer patients and disease prognosis

Authors: Kutilin D.S.¹, Frantsiyants E.M.¹, Neskubina I.V.¹, Shikhlyarova A.I.¹, Bandovkina V.A.¹, Kachesova P.S.¹, Cheryarina N.D.¹, Udalenkova I.A.¹, Menshenina A.P.¹, Ozerkova E.A.¹, Shatova Y.S.¹, Ovsyannikova A.A.¹
Affiliations:
1. National Medical Research Center of Oncology, Ministry of Health of Russia
Issue: Vol 13, No 3 (2026)
Pages: 8-19
Section: RESEARCH ARTICLES
Published: 18.09.2026
URL: https://umo.abvpress.ru/jour/article/view/859
DOI: https://doi.org/10.17650/2313-805X-2026-13-3-8-19
ID: 859

Cite item

Full Text

Open Access
Restricted Access

Access granted
Restricted Access

Subscription or Fee Access

Abstract
About the authors
References
Supplementary files
Statistics

Abstract

Introduction. Uterine cancer is a leading gynecologic oncology morbidity. Early prediction of metastatic disease is critical for treatment decisions. Therefore, the search for minimally invasive molecular markers for predicting metastasis is a pressing issue. Promising biomarkers in this regard include gene copy number values in circulating cell-free DNA (cfDNA) in plasma.

Aim. To analyze the relative copy number of genes regulating mitochondrial function in plasma of uterine cancer patients to develop a minimally invasive method for predicting metastasis.

Materials and methods. The bioinformatics phase of the study identified a list of genes associated with mitochondrial dysfunction and abnormal copy number in uterine cancer. The study included 98 patients diagnosed with adenocarcinoma of the corpus uteri (G₁ (n = 43), G₂ (n = 35) and G₃ (n = 20)), 15 patients with uterine myoma and 20 conditionally healthy donors. The relative copy number of 13 genes was determined by quantitative real-time polymerase chain reaction on cfDNA samples from blood plasma. ROC analysis and LASSO-penalized (LASSO – Least Absolute Shrinkage and Selection Operator) logistic regression were used to select markers.

Results. A significant decrease in relative copy number of mtSSB, MT-RNR2, NRF1, MGME1, and MT-CO1 in plasma was revealed in uterine cancer patients (p <0.005) with a metastatic course of the disease, moreover, the degree of change in copy number increased from G₁ to G₃. LASSO regression analysis enabled the selection of three genes: mtSSB, MT-RNR2, and MGME1. The combined panel achieved an area under the curve (AUC) of 0.98 (95 % confidence interval 0.96–1.00), a sensitivity of 95 %, and a specificity of 92 % for predicting metastases.

Conclusion. Thus, determination of the copy number of the mtSSB, MT-RNR2 and MGME1 genes in blood plasma has potential for use in minimally invasive prediction of metastatic lesions in uterine cancer.

Keywords

endometrial cancer, cell-free DNA, gene copy number, LASSO regression, mitochondrial dysfunction, metastasis prediction

References

Crosbie E.J., Kitson S.J., McAlpine J.N. et al. Endometrial cancer. Lancet 2022;399(10333):1412–28. doi: 10.1016/S0140-6736(22)00323-3
Concin N., Matias-Guiu X., Vergote I. et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Radiother Oncol 2021;154:327–53. doi: 10.1016/j.radonc.2020.11.018
Maslov A.A., Chalkhakhian L.H., Malinin S.A. et al. Gene copy number in patients with colorectal cancer as a marker of clinical outcome of the disease and response to therapy. Yuzhno-rossiyskiy onkologicheskiy zhurnal = South Russian Journal of Oncology 2022;3(2):52–64. (In Russ.).
Hastings P.J., Lupski J.R., Rosenberg S.M., Ira G. Mechanisms of change in gene copy number. Nat Rev Genet 2009;10(8):551–64. doi: 10.1038/nrg2593
Steele C.D., Abbasi A., Islam S.M.A. et al. Signatures of copy number alterations in human cancer. Nature 2022;606(7916):984–91. doi: 10.1038/s41586-022-04738-6
Wallace D.C. Mitochondria and cancer. Nat Rev Cancer 2012;12(10):685–98. doi: 10.1038/nrc3365
Kit O.I., Vodolazhsky D.I., Kutilin D.S. et al. Copy number of GSTP1, NFKB1 genes and mitochondrial DNA HV2 locus in some histological types of stomach cancer. Uspekhi sovremennogo estestvoznaniya = Advances in Modern Natural Sciences 2015;1–6:918–21. (In Russ.).
Kutilin D.S., Airapetova T.G., Anistratov P.A. et al. Changes in the relative copy number of genetic loci in extracellular DNA in patients with adenocarcinoma of the lung. Izvestiya vuzov. Severo-Kavkazskiy region. Estestvennye nauki = University News. North Caucasus Region. Natural Sciences 2017;3:74–83. (In Russ.).
Xu Y., Zhou J., Yuan Q. et al. Quantitative detection of circulating MT-ND1 as a potential biomarker for colorectal cancer. Bosn J Basic Med Sci 2021;21(5):577–86. doi: 10.17305/bjbms.2021.5576
Tsandekova M.R., Porkhanova N.V., Kutilin D.S. Molecular subtypes of ovarian serous adenocarcinoma and patient survival. Onkoginekologiya = Oncogynecology 2022;4(44):14–24. (In Russ.). doi: 10.52313/22278710_2022_4_4
Kit O.I., Frantsiyants E.M., Kaplieva I.V. et al. Features of mitochondrial genes copy numbers and microRNA transcripts in endometrial adenocarcinoma and fibroids patients blood plasma. uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology 2025;12(1):76–83. (In Russ.). doi: 10.17650/2313-805X-2025-12-1-76-8
Kutilin D.S., Frantsians E.M., Neskubina I.V. et al. Features of gene copy number regulating the functioning of mitochondria in patients with uterine body cancer with type 2 diabetes mellitus. Sovremennye problemy nauki i obrazovaniya = Modern Problems of Science and Education 2025;5. (In Russ.). doi: 10.17513/spno.34316
Kutilin D.S., Kecheryukova M.M. From bioinformatics screening of genetic markers to minimally invasive diagnosis of lymph node metastases in patients with cervical cancer. Kazanskiy medicinskiy zhurnal = Kazan Medical Journal 2022;103(5):725–36. doi: 10.17816/KMJ2022-725
Xu Y.C., Su J., Zhou J.J. et al. Roles of MT-ND1 in cancer. Curr Med Sci 2023;43(5):869–78. doi: 10.1007/s11596-023-2771-0
Cameron S.L., Yoshizawa K., Mizukoshi A. et al. Mitochondrial genome deletions and minicircles are common in lice (Insecta: Phthiraptera). BMC Genomics 2011;12:394. doi: 10.1186/1471-2164-12-394
Kang S., Kim Y. Current unveiling key research trends in endometrial cancer. Healthcare 2025;13(13):1567. doi: 10.3390/healthcare13131567
Njomen E., Evans H.G., Gedara S.H., Heyl D.L. Humanin peptide binds to insulin-like growth factor-binding protein 3 (IGFBP3) and regulates its interaction with importin-β. Protein Pept Lett 2015;22(10):869–76. doi: 10.2174/0929866522666150728114955
Uhler J.P., Thörn C., Nicholls T.J. et al. MGME1 processes flaps into ligatable nicks in concert with DNA polymerase γ during mtDNA replication. Nucleic Acids Res 2016;44(12):5861–71. doi: 10.1093/nar/gkw468

Supplementary files

Supplementary Files

Action

1. JATS XML

Download

Username
Password
Remember me

Forgot password?	Register

Username
Password
Remember me

Forgot password?	Register

The genes copy number variation features in blood plasma of uterine cancer patients and disease prognosis

Full Text

Abstract

Keywords

About the authors

References

Supplementary files