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