Features of the expression of the molecular chaperones Hsp27 and Hsp90 in serous ovarian cancer
https://doi.org/10.31549/2542-1174-2025-9-2-7-18
Abstract
I n t r o d u c t i o n . Ovarian cancer (OC) represents the second most common cause of death from gynecologic cancer, with serous cancer being the most common and aggressive of all histologic variants. The search for new biomarkers and therapeutic targets for the OC treatment is an urgent task of gynecologic oncology. In recent years, researchers have focused their attention on the study of heat shock proteins (Hsps), which are molecular chaperones synthesized in response to stress factors exposure and contributing to the refolding of damaged proteins and restoring their cellular functions. Molecular chaperones are involved in maintaining cell homeostasis, regulating the activity of oncogenes and tumor suppressors.
A i m . To study the features of the Hsp27 and Hsp90 expression in serous OC compared with borderline ovarian tumors, taking into account the intracellular localization and the potential diagnostic value of these markers.
M a t e r i a l s a n d m e t h o d s . The study included 23 patients with newly diagnosed serous OC and 6 women with FIGO stage I–IIIC borderline ovarian tumors (mean age 53,4 ± 8,1 years) who were treated at the Tomsk Research Institute of Oncology and/or Tomsk Regional Oncological Center. The study objects were paraffin blocks from tumor tissue obtained during biopsy and surgery intervention during laparoscopic surgical staging before the treatment. The intracellular localization of Hsp27 and Hsp90 in tumor and stromal cells was determined by immunohistochemical (IHC) staining.
R e s u l t s . The IHC study revealed that the expression of Hsp27 in tumor cells, when calculated by cytoplasm and nucleus, is 10,48 and 7,41 times higher than in the stroma, respectively; the expression of Hsp90 in tumor cells is 40,42 and 86,67 times higher in cytoplasm and nuclei than in stromal cells, respectively. The count of Hsp27-positive tumor cells is 3,2 times higher than the count of Hsp90-positive tumor cells in tissue of ovarian serous adenocarcinoma (p = 0,0006, Wilcoxon test). In borderline ovarian tumors, the count of Hsp27- and Hsp90-positive tumor cells is significantly lower than in OC (p < 0,0001 and p = 0,0018, respectively, Mann-Whitney test).
C o n c l u s i o n . The significant difference in the expression of the molecular chaperones Hsp27 and Hsp90 in the cellular compartments of tumor and stromal cells, as well as a more than fourfold increase in this marker in serous ovarian carcinoma compared with borderline tumors show the diagnostic and prognostic role of Hsp27 and Hsp90 in the immunohistochemical diagnosis of OC, as well as the prospects of Hsp27 and Hsp90 activity modulation targeted therapy.
About the Authors
E. V. KaigorodovaRussian Federation
Evgeniya V. Kaigorodova – Dr. Sci. (Med.), Associate Professor, Leading Researcher, Department of General and Molecular Pathology; Professor, Departments of Biochemistry and Molecular Biology with a Course of Clinical Laboratory Diagnostics
Researcher ID: A-5400-2014
Scopus ID: 24778286000
2, Moskovskiy trakt, Tomsk, 634050
O. I. Kovalev
Russian Federation
Oleg I. Kovalev – Post-graduate Student, Departments of Pathological Anatomy
Researcher ID: ABC-8699-2020
Tomsk
M. Yu. Grishchenko
Russian Federation
Maxim Y. Grishchenko – Cand. Sci. (Med.), Head, Department of Surgery with a Сourse of Mobilization Training and Disaster Medicine; Chief Physician
Tomsk
S. V. Vtorushin
Russian Federation
Sergey V. Vtorushin – Dr. Sci. (Med.), Professor, Deputy Director for Research and Translational Medicine, Head, Department of General and Molecular Pathology; Professor, Department of Pathological Anatomy
Researcher ID: S-3789-2016
Tomsk
References
1. Momenimovahed Z., Tiznobaik A., Taheri S., Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors // Int. J. Women’s Health. 2019;11:287-299. DOI: 10.2147/IJWH.S197604.
2. Torre L.A., Trabert B., DeSantis C.E. et al. Ovarian cancer statistics, 2018 // CA Cancer J. Clin. 2018;68(4):284-296. DOI: 10.3322/caac.21456.
3. Elias K.M., Guo J., Bast R.C. Jr. Early detection of ovarian cancer // Hematol. Oncol. Clin. North Am. 2018;32(6):903-914. DOI: 10.1016/j.hoc.2018.07.003.
4. Nebgen D.R., Lu K.H., Bast R.C. Jr. Novel approaches to ovarian cancer screening // Curr. Oncol. Rep. 2019;21(8):75. DOI: 10.1007/s11912-019-0816-0.
5. Lucidi A., Buca D., Ronsini C. et al. Role of extracellular vesicles in epithelial ovarian cancer: A systematic review // Int. J. Mol. Sci. 2020;21(22):8762. DOI: 10.3390/ijms21228762.
6. Hrudka J., Jelínková K., Fišerová H. et al. Heat shock proteins 27, 70, and 110: Expression and prognostic significance in colorectal cancer // Cancers (Basel). 2021; 13(17):4407. DOI: 10.3390/cancers13174407.
7. Kaigorodova E.V., Bogatyuk M.V. Heat shock proteins as prognostic markers of cancer // Curr. Cancer Drug Targets. 2014;14(8):713-726. DOI: 10.2174/1568009614666140926122846.
8. Hu C., Yang J., Qi Z. et al. Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities // MedComm(2020). 2022;3(3):e161. DOI: 10.1002/mco2.161.
9. Langdon S.P., Rabiasz G.J., Hirst G.L. et al. Expression of the heat shock protein HSP27 in human ovarian cancer // Clin. Cancer Res. 1995;1(12):1603-1609.
10. Cheng Q., Chang J.T., Geradts J. Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer // Breast Cancer Res. 2012;14(2):R62.
11. Solit D.B., Chiosis G. Development and application of Hsp90 inhibitors // Drug Discov. Today. 2008;13(1-2):38-43.
12. Calderwood S.K., Khaleque M.A., Sawyer D.B., Ciocca D.R. Heat shock proteins in cancer: chaperones of tumorigenesis // Trends Biochem. Sci. 2006;31(3):164-172.
13. Bankhead P., Loughrey M.B., Fernández J.A. et al. QuPath: Open source software for digital pathology image analysis // Sci. Rep. 2017;7(1):16878. DOI: 10.1038/s41598-017-17204-5.
14. Liu C.C., Chou K.T., Hsu J.W. et al. High metabolic rate and stem cell characteristics of esophageal cancer stem-like cells depend on the Hsp27-AKT-HK2 pathway // Int. J. Cancer. 2019;145(8):2144-2156. DOI: 10.1002/ijc.32301.
15. Kabakov A., Yakimova A., Matchuk O. Molecular chaperones in cancer stem cells: Determinants of stemness and potential targets for antitumor therapy // Cells. 2020; 9(4):892. DOI: 10.3390/cells9040892.
16. Mellier G., Liu D., Bellot G. et al. Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27 // Cell Death Dis. 2013;4(10):e890. DOI: 10.1038/cddis.2013.413.
17. Lampros M., Vlachos N., Voulgaris S., Alexiou G.A. The role of Hsp27 in chemotherapy resistance // Biomedicines. 2022;10(4):897. DOI: 10.3390/biomedicines10040897.
18. Su J.M., Hsu Y.Y., Lin P., Chang H. Nuclear accumulation of heat-shock protein 90 is associated with poor survival and metastasis in patients with non-small cell lung cancer // Anticancer Res. 2016;36(5):2197-2203.
19. Stope M.B., Klinkmann G., Diesing K. et al. (2017). Heat shock protein HSP27 secretion by ovarian cancer cells is linked to intracellular expression levels, occurs independently of the endoplasmic reticulum pathway and HSP27's phosphorylation status, and is mediated by exosome liberation // Dis. Markers. 2017;2017:1575374. DOI: 10.1155/2017/1575374.
20. Kaigorodova E.V., Ryazantseva N.V., Novitsky V.V. (2012). Apoptosis and Heat Shock Proteins. Tomsk. 188 p. (In Russ.)
Review
For citations:
Kaigorodova E.V., Kovalev O.I., Grishchenko M.Yu., Vtorushin S.V. Features of the expression of the molecular chaperones Hsp27 and Hsp90 in serous ovarian cancer. Journal of Siberian Medical Sciences. 2025;(2):7-18. (In Russ.) https://doi.org/10.31549/2542-1174-2025-9-2-7-18