Preview

Research and Practical Medicine Journal

Advanced search

Features of some growth factors content in tumors and blood plasma in patients with rare forms of endometrial cancer

https://doi.org/10.17709/2410-1893-2025-12-2-2

EDN: EARGNT

Abstract

Purpose of the study. The objective of the present study was to examine the levels of TGFβ1, EGF, and EGFR in the blood and tissue of morphologically distinct endometrial tumors, including uterine serous carcinoma (USC), clear cell endometrial cancer (CCEC), and G3 endometrioid adenocarcinoma (EAC).
Patients and methods. The study encompassed 61 patients diagnosed with uterine body cancer, including 21 patients with USC, 20 patients with CCEC, and 20 patients with EAC (G3). All patients underwent a thorough morphological verification of the disease, as documented in the postoperative report. The level of epidermal growth factor and its receptor (EGF and EGFR), as well as transforming growth factor (TGFb1), was determined in cytosolic fractions of 10 % tumor homogenates and blood samples using standard ELISA kits. Samples of intact endometrium obtained from patients who underwent surgery for uterine fibroids (n = 20) and blood samples from conditionally healthy women (n = 20) of the same age served as normal indicators. Statistical analysis of the results was performed using the Statistica 10.0 software package.
Results. EAC (G3) was characterized by an increased, compared to the healthy, content of growth factors and their receptors in tumor and blood samples. In tumor samples of CCEC and USC, the level of TGFβ1 was lower by 2.2 times and 1.6 times, respectively, and the concentration of EGF was on average more than 2 times lower, compared to the indicators in the intact endometrium. The content of these same growth factors in blood samples in patients with rare forms of EC exceeded the normative values by 2.1–4.2 times.
Conclusion. The investigation revealed that low levels of EGF were present in tumor samples of rare forms of endometrial cancer, accompanied by unaltered levels of EGFR and TGFβ1. This observation stands in contrast to the elevated concentrations of these growth factors detected in blood samples. The distinctive profile of these growth factors in tumor samples differentiates them from the indicators observed in EAC tissue, where the levels of EGFR and TGFβ1 are augmented. It is plausible that the altered metabolism of non-endometrioid uterine cancers leads to alterations in the biological characteristics of tumors, consequently resulting in a more aggressive clinical course.

About the Authors

E. M. Frantsiyants
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Elena M. Frantsiyants – Dr. Sci. (Biology), Professor, Deputy General Director for Science, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: http://orcid.org/0000-0003-3618-6890

eLibrary SPIN: 9427-9928, AuthorID: 462868

Scopus Author ID: 55890047700

Web of Science Researcher ID: Y-1491-2018


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



V. A. Bandovkina
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Valerija A. Bandovkina – Dr. Sci. (Biology), Leading Researcher at Laboratory of Malignant Tumor Pathogenesis Study, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: http://orcid.org/0000-0002-2302-8271

eLibrary SPIN: 8806-2641, Author ID: 696989

Scopus Author ID: 57194276288

Web of Science Researcher ID: AAG-8708-2019


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



T. I. Moiseenko
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Tatiana I. Moiseenko – Dr. Sci. (Medicine), Professor, Chief Researcher at the Department of Oncogynecology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0003-4037-7649

eLibrary SPIN: 6341-0549, AuthorID: 705829

Scopus Author ID: 57194270696


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



A. P. Menshenina
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Anna P. Menshenina – Dr. Sci. (Medicine), Associate Professor, Leading Researcher at the Department of Oncogynecology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: http://orcid.org/0000-0002-7968-5078

eLibrary SPIN: 6845-4794, AuthorID: 715810

Scopus Author ID: 57191983118


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



M. A. Rogozin
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Mark A. Rogozin – graduate student, Section of Reproductive Tumors, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0009-0003-7909-2883

eLibrary SPIN: 3965-1806, AuthorID: 1238353


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



I. V. Kaplieva
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Irina V. Kaplieva – Dr. Sci. (Medicine), Head of the Laboratory of Malignant Tumor Pathogenesis Study, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0002-3972-2452

eLibrary SPIN: 5047-1541, AuthorID: 734116

Scopus Author ID: 23994000800

Web of Science ResearcherID: AAE-3540-2019


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



E. I. Surikova
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Ekaterina I. Surikova – Cand. Sci. (Biology), Senior Researcher at Laboratory of Malignant Tumor Pathogenesis Study, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0002-4318-7587

eLibrary SPIN: 2401-4115, AuthorID: 301537

Scopus Author ID: 6507092816

Web of Science ResearcherID: AAG-8748-2019


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



I. V. Neskubina
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Irina V. Neskubina – Dr. Sci. (Biology), Senior Researcher at Laboratory of Malignant Tumor Pathogenesis Study, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0002-7395-3086

eLibrary SPIN: 3581-8531, Author ID: 794688

Scopus Author ID: 6507509066


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



Yu. A. Petrova
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Yulia A. Petrova – Cand. Sci. (Biology), Senior Researcher at Laboratory of Malignant Tumor Pathogenesis Study, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: http://orcid.org/0000-0002-2674-9832

eLibrary SPIN: 2168-8737, AuthorID: 558241

Scopus Author ID: 37026863400

Web of Science ResearcherID: AAE-4168-2022


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



N. D. Cheryarina
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Nataliya D. Cheryarina – laboratory assistant at Laboratory of Malignant Tumor Pathogenesis Study, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0002-3711-8155

eLibrary SPIN: 2189-3404, AuthorID: 558243

Scopus Author ID: 56204439400


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



M. L. Adamyan
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Meri L. Adamyan – Cand. Sci. (Medicine), researcher, Department of Oncogynecology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0003-4188-3746

eLibrary SPIN: 9929-3414, AuthorID: 710702

Scopus Author ID: 58579808700


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



O. E. Zhenilo
https://rnioi.ru
National Medical Research Centre for Oncology

Rostov-on-Don, Russian Federation

 

Oksana E. Zhenilo – Cand. Sci. (Medicine), researcher, Department of Oncogynecology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0002-9833-8530

eLibrary SPIN: 4078-7080, AuthorID: 732220


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



A. O. Adamyan
https://rostgmu.ru
Rostov State Medical University

Rostov-on-Don, Russian Federation

 

Alla O. Adamyan – student, Rostov State Medical University, Rostov-on-Don, Russian Federation

ORCID: http://orcid.org/0009-0006-5101-7509


Competing Interests:

The author declares that there are no obvious and potential conflicts of interest related to the publication of this article.



References

1. Galant N, Krawczyk P, Monist M, Obara A, Gajek Ł, Grenda A, et al. Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection. Int J Mol Sci. 2024 May 28;25(11):5893. https://doi.org/10.3390/ijms25115893

2. Suarez AA, Felix AS, Cohn DE. Bokhman Redux: Endometrial cancer "types" in the 21st century. Gynecol Oncol. 2017 Feb;144(2):243– 249. https://doi.org/10.1016/j.ygyno.2016.12.010

3. Connor EV, Rose PG. Management Strategies for Recurrent Endometrial Cancer. Expert Rev Anticancer Ther. 2018 Sep;18(9):873– 885. https://doi.org/10.1080/14737140.2018.1491311

4. Larish A, Mariani A, Langstraat C. Controversies in the Management of Early-stage Serous Endometrial Cancer. In Vivo. 2021 MarApr;35(2):671–680. https://doi.org/10.21873/invivo.12307

5. Zhang M, Yang TJ, Desai NB, DeLair D, Kollmeier MA, Makker V, et al. Comparison of outcomes in early-stage uterine clear cell carcinoma and serous carcinoma. Brachytherapy. 2019 Jan-Feb;18(1):38–43. https://doi.org/10.1016/j.brachy.2018.08.015

6. Hilage P, Birajdar A, Marsale T, Patil D, Patil AM, Telang G, Somasundaram I, Sharma RK, Joshi MG. Characterization and angiogenic potential of CD146+ endometrial stem cells. Stem Cell Res Ther. 2024 Sep 27;15(1):330. https://doi.org/10.1186/s13287-024-03918-7

7. Yen TT, Wang TL, Fader AN, Shih IM, Gaillard S. Molecular Classification and Emerging Targeted Therapy in Endometrial Cancer. Int J Gynecol Pathol. 2020 Jan;39(1):26–35. https://doi.org/10.1097/pgp.0000000000000585

8. Farooqi AA, Turgambayeva A, Tashenova G, Tulebayeva A, Bazarbayeva A, Kapanova G, Abzaliyeva S. Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis. Molecules. 2022 Dec 21;28(1):67. https://doi.org/10.3390/molecules28010067

9. Köstler WJ, Zeisel A, Körner C, Tsai JM, Jacob-Hirsch J, Ben-Chetrit N, et al. Epidermal growth-factor-induced transcript isoform variation drives mammary cell migration. PLoS One. 2013 Dec 6;8(12):e80566. https://doi.org/10.1371/journal.pone.0080566

10. Uribe ML, Marrocco I, Yarden Y. EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance. Cancers (Basel). 2021 Jun 1;13(11):2748. https://doi.org/10.3390/cancers13112748

11. Shevchenko AN, Breus AA, Neskubina IV, Dzhenkova EA, Filatova EV, Shvyrev DA. Evaluation of the prognostic significance of some biological factors in local and generalized clear cell renal cancer. South Russian Journal of Cancer. 2020;1(1):6–22. https://doi.org/10.37748/2687-0533-2020-1-1-1

12. Albitar L, Pickett G, Morgan M, Wilken JA, Maihle NJ, Leslie KK. EGFR isoforms and gene regulation in human endometrial cancer cells. Mol Cancer. 2010 Jun 25;9:166. https://doi.org/10.1186/1476-4598-9-166

13. Kit OI, Kodonidi IP, Frantsiyants EM, Kaplieva IV, Glushko AA, Trepitaki LK, et al. Antitumor effect of a new human epidermal growth factor receptor inhibitor. Research and Practical Medicine Journal. Research and Practical Medicine Journal. 2024;11(3):54–64. (In Russ.). https://doi.org/10.17709/2410-1893-2024-11-3-4 EDN: TKJEHK

14. Figueiredo AS, Schumacher A. The T helper type 17/regulatory T cell paradigm in pregnancy. Immunology. 2016 May;148(1):13–21. https://doi.org/10.1111/imm.12595 Erratum in: Immunology. 2019 Feb;156(2):213. https://doi.org/10.1111/imm.13014

15. Frantsiyants EM, Samaneva NYu, Vladimirova LYu, Storozhakova AE, Kalabanova EA, Kabanov SN, Tishina AV. Blood levels of growth and progression factors in patients with locally advanced breast cancer during neoadjuvant chemotherapy. South Russian Journal of Cancer. 2021;2(3):6–12. https://doi.org/10.37748/2686-9039-2021-2-3-1

16. Xue F, Liu L, Tao X, Zhu W. TET3-mediated DNA demethylation modification activates SHP2 expression to promote endometrial cancer progression through the EGFR/ERK pathway. J Gynecol Oncol. 2024 Sep;35(5):e64. https://doi.org/10.3802/jgo.2024.35.e64

17. Wang Y, Shu H, Liu J, Jin X, Wang L, Qu Y, et al. EGF promotes PKM2 O-GlcNAcylation by stimulating O-GlcNAc transferase phosphorylation at Y976 and their subsequent association. J Biol Chem. 2022 Sep;298(9):102340. https://doi.org/10.1016/j.jbc.2022.102340

18. Wang P, Zhang T, Jiang N, Wang K, Feng L, Liu T, Yang X. PDIA6, which is regulated by TRPM2-AS/miR-424-5p axis, promotes endometrial cancer progression via TGF-beta pathway. Cell Death Dis. 2023 Dec 14;14(12):829. https://doi.org/10.1038/s41419-023-06297-8

19. Papageorgiou D, Liouta G, Sapantzoglou I, Zachariou E, Pliakou D, Papakonstantinou K, et al. HER2-Positive Serous Endometrial Cancer Treatment: Current Clinical Practice and Future Directions. Medicina (Kaunas). 2024 Dec 6;60(12):2012. https://doi.org/10.3390/medicina60122012

20. Vermij L, Horeweg N, Leon-Castillo A, Rutten TA, Mileshkin LR, Mackay HJ, et al. HER2 Status in High-Risk Endometrial Cancers (PORTEC-3): Relationship with Histotype, Molecular Classification, and Clinical Outcomes. Cancers (Basel). 2020 Dec 25;13(1):44. https://doi.org/10.3390/cancers13010044

21. Buza N, Euscher ED, Matias-Guiu X, McHenry A, Oliva E, Ordulu Z, Parra-Herran C, Rottmann D, Turner BM, Wong S, Hui P. Reproducibility of scoring criteria for HER2 immunohistochemistry in endometrial serous carcinoma: a multi-institutional interobserver agreement study. Mod Pathol. 2021 Jun;34(6):1194–1202. https://doi.org/10.1038/s41379-021-00746-5

22. Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, et al. Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clin Cancer Res. 2020 Aug 1;26(15):3928–3935. https://doi.org/10.1158/1078-0432.ccr-20-0953

23. Valastyan S, Weinberg RA. Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011 Oct 14;147(2):275–292. https://doi.org/10.1016/j.cell.2011.09.024

24. Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol. 2019 Jul 12;12(1):76. https://doi.org/10.1186/s13045-019-0760-3

25. Carmeliet P, Jain RK. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011 Jun;10(6):417–427. https://doi.org/10.1038/nrd3455

26. Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, Segall JE, Pollard JW, Condeelis J. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 2007 Mar 15;67(6):2649–2656. https://doi.org/10.1158/0008-5472.can-06-1823

27. Lin Y, Wang X, Jin H. EGFR-TKI resistance in NSCLC patients: mechanisms and strategies. Am J Cancer Res. 2014 Sep 6;4(5):411–435.

28. Klein CA. Parallel progression of primary tumours and metastases. Nat Rev Cancer. 2009 Apr;9(4):302–312. https://doi.org/10.1038/nrc2627

29. Hüsemann Y, Geigl JB, Schubert F, Musiani P, Meyer M, Burghart E, Forni G, Eils R, Fehm T, Riethmüller G, Klein CA. Systemic spread is an early step in breast cancer. Cancer Cell. 2008 Jan;13(1):58–68. https://doi.org/10.1016/j.ccr.2007.12.003

30. Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambardzumyan D, Varmus H. Seeding and propagation of untransformed mouse mammary cells in the lung. Science. 2008 Sep 26;321(5897):1841–1844. https://doi.org/10.1126/science.1161621


Review

For citations:


Frantsiyants E.M., Bandovkina V.A., Moiseenko T.I., Menshenina A.P., Rogozin M.A., Kaplieva I.V., Surikova E.I., Neskubina I.V., Petrova Yu.A., Cheryarina N.D., Adamyan M.L., Zhenilo O.E., Adamyan A.O. Features of some growth factors content in tumors and blood plasma in patients with rare forms of endometrial cancer. Research and Practical Medicine Journal. 2025;12(2):23-34. (In Russ.) https://doi.org/10.17709/2410-1893-2025-12-2-2. EDN: EARGNT

Views: 116


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2410-1893 (Online)