Insulin-like growth factors and their transfer protein in the blood of patients with primary and recurrent soft tissue sarcomas
- Authors: Goroshinskaya I.A.1, Kaplieva I.V.1, Sagatelyan S.A.1, Frantsiyants E.M.1, Vashchenko L.N.1, Pogorelova Y.A.1, Nemashkalova L.A.1, Ausheva T.V.1, Chernogorov P.V.1, Trepitaki L.K.1, Sheiko E.A.1, Pandova O.V.1
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Affiliations:
- National Medical Research Centre of Oncology, Ministry of Health of Russia
- Issue: Vol 14, No 4 (2022)
- Pages: 45-53
- Section: SOFT TISSUE SARCOMAS
- Published: 21.12.2022
- URL: https://sarbon.abvpress.ru/jour/article/view/590
- DOI: https://doi.org/10.17650/2782-3687-2022-14-4-45-53
- ID: 590
Cite item
Full Text
Abstract
Introduction. Soft tissue sarcomas (STS) are rare diseases but their characteristic tendency for recurrence and high mortality dictate the need for the search for prognostic biomarkers for identification of patients with the risk of recurrence. In this context, the system of insulin-like growth factors (IGF) and their insulin-like growth factor-binding proteins (IGFBP) is of interest because it was shown that disruption of the IGF system regulation leads to cancer cell proliferation and migration and chemotherapy resistance.
The study objective is to investigate the levels of the IGF system components in blood of patients with primary and recurrent STS.
Materials and methods. In total, 54 patients with STS, T2bN0M0, were examined: 12 men and 12 women with primary STS, 10 men and 20 women with recurrent STS, as well as healthy donors (10 men and 10 women). Mean patient age was 63.1 ± 0.9 years. In blood sampled prior to treatment, the levels of insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2) and insulin-like growth factor-binding protein 2 (IGFBP2) were measured by ELISA using Mediagnost kits (Germany). Statistical analysis was performed using Statistica 10 software and non-parametric Mann-Whitney test.
Results. In primary STS, the levels of IGF1 in men with G3–4 tumors and all women decreased 14- and 20-fold, respectively, compared to healthy donors. Additionally, an insignificant decrease of IGF2 level in men and a decrease of IGF1/IGF2 ratio by the factor of 8.8 in men with G3–4 tumors and by the factor of 24.3 in women were observed. In recurrences, IGF1 level decreased by 40 % in men and by 78–85.5 % in women, while IGF2 level in men with G3–4 tumors decreased by 19 %, in women increased by 21–58 % compared to donors. In women with primary STS and recurrences of G3–4 tumors, IGFBP2 was also elevated. In men with G3–4 tumors, changes in IGFBP2 levels were less significant and had an opposite trend compared to women.
Conclusion. STS recurrence is accompanied by imbalance of IGF system components in blood, especially in patients of both sexes with G3–4 tumors. Correlation between increased IGFBP2 level in STS and clinical characteristics of the disease, especially in recurrence, suggest prognostic significance of this molecule.
About the authors
I. A. Goroshinskaya
National Medical Research Centre of Oncology, Ministry of Health of Russia
Author for correspondence.
Email: iagor17@mail.ru
ORCID iD: 0000-0001-6265-8500
63 14thliniya, Rostov-on-Don 344037
Russian FederationI. V. Kaplieva
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-3972-2452
63 14thliniya, Rostov-on-Don 344037
S. A. Sagatelyan
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0003-2854-8716
63 14thliniya, Rostov-on-Don 344037
E. M. Frantsiyants
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0003-3618-6890
63 14thliniya, Rostov-on-Don 344037
L. N. Vashchenko
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-7302-7031
63 14thliniya, Rostov-on-Don 344037
Yu. A. Pogorelova
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-2674-9832
63 14thliniya, Rostov-on-Don 344037
L. A. Nemashkalova
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0003-2713-8598
63 14thliniya, Rostov-on-Don 344037
T. V. Ausheva
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-7073-9463
63 14thliniya, Rostov-on-Don 344037
P. V. Chernogorov
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-1202-497X
63 14thliniya, Rostov-on-Don 344037
L. K. Trepitaki
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-9749-2747
63 14thliniya, Rostov-on-Don 344037
E. A. Sheiko
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0002-9616-8996
63 14thliniya, Rostov-on-Don 344037
O. V. Pandova
National Medical Research Centre of Oncology, Ministry of Health of Russia
ORCID iD: 0000-0003-2218-9345
63 14thliniya, Rostov-on-Don 344037
References
- Gamboa A.C., Gronchi A., Cardona K. Soft-tissue sarcoma in adults: an update on the current state of histiotype-specific management in an era of personalized medicine. CA Cancer J Clin 2020;70(3):200–29. doi: 10.3322/caac.21605
- Roszik J., Mustachio L.M., Livingston J.A. et al. Landscape of immunerelated markers and potential therapeutic targets in soft tissue sarcoma. Cancers (Basel) 2021;13(20):5249. doi: 10.3390/cancers13205249
- Pillozzi S., Bernini A., Palchetti I. et al. Soft tissue sarcoma: an insight on biomarkers at molecular, metabolic and cellular level. Cancers (Basel) 2021;13(12):3044. doi: 10.3390/cancers13123044
- Kit O.I., Frantsiyants E.M., Bandovkina V.A. et al.The level of sex hormones and prolactin in the tissue of malignant breast tumors in patients of different ages. Fundamental'nye issledovaniya = Fundamental Research 2013;7(3):560–4. (In Russ.).
- Franzyants E.M., Khamaneva N.Yu., Vladimirova L.Yu. et al. The content of growth and progression factors in the blood of patients with locally advanced breast cancer during neoadjuvant chemotherapy. Yuzhnorossijskij onkologicheskij zhurnal = South Russian Journal of Oncology 2021;2(3):6–12. (In Russ.). doi: 10.37748/2686-9039-2021-2-3-1
- Mancarella C., Morrione A., Scotlandi K. Unraveling the IGF system interactome in sarcomas exploits novel therapeutic options. Cells 2021;10(8):2075. doi: 10.3390/cells10082075
- Cao J., Yee D. Disrupting insulin and IGF receptor function in cancer. Int J Mol Sci 2021;22(2):555. doi: 10.3390/ijms22020555
- Majchrzak-Baczmańska D., Malinowski A., Głowacka E., Wilczyński M. Does IGF-1 play a role in the biology of ovarian cancer? Ginekologia Polska 2018;89(1):13–9. doi: 10.5603/GP.a2018.0003
- Rodríguez-Valentín R., Torres-Mejía G. et al. Energy homeostasis genes modify the association between serum concentrations of IGF-1 and IGFBP-3 and breast cancer risk. Sci Rep 2022;12(1):1837. doi: 10.1038/s41598-022-05496-1
- Kalledsøe L., Dragsted L.O., Hansen L. et al. The insulin-like growth factor family and breast cancer prognosis: A prospective cohort study among postmenopausal women in Denmark. Growth Horm IGF Res 2019;4:33–42. doi: 10.1016/j.ghir.2018.12.003
- Damerell V., Pepper M.S., Prince S. Molecular mechanisms underpinning sarcomas and implications for current and future therapy. Signal Transduct Target Ther 2021;6(1):246. doi: 10.1038/s41392-021-00647-8
- Frantsiyants E.M., Bandovkina V.A., Kaplieva I.V. et al. Insulin-like growth factors and their binding proteins in the heart in rats in experimental diabetes mellitus, growing Guerins carcinoma and under their combination. Cardiometry 2021;18:138–44. doi: 10.18137/cardiometry.2021.18.138144
- Frantsiyants E.M., Bandovkina V.A., Kaplieva I.V. et al. Insulin-like growth factors and their carrier proteins in the liver of rats with experimental diabetes, malignant growth of uterine adenocarcinoma and their combination. Byulleten' sibirskoj mediciny = Bulletin of Siberian Medicine 2022;21(2):129–36. (In Russ.). doi: 10.20538/1682-0363-2022-2-129-136
- Frantsiyants E.M., Bandovkina V.A., Kaplieva I.V. et al. Insulin-like growth factors and their carrier proteins in kidneys of rats with experimental diabetes, malignant tumor, and their combination. Byulleten’ sibirskoj mediciny = Bulletin of Siberian Medicine 2022;21(3):112–9. (In Russ.). DOI: /10.20538/1682-0363-2022-3-112-119
- Tang D., Yao R., Zhao D. et al. Trichostatin A reverses the chemoresi-stance of lung cancer with high IGFBP2 expression through enhancing autophagy. Sci Rep 2018;8:3917. doi: 10.1038/s41598-018-22257-1
- Kashyap M.K. Role of insulin-like growth factor-binding proteins in the pathophysiology and tumorigenesis of gastroesophageal cancers. Tumour Biol 2015;36(11):8247–57. doi: 10.1007/s13277-015-3972-3
- Pohlman A.W., Moudgalya H., Jordano L. et al. The role of IGFpathway biomarkers in determining risks, screening, and prognosis in lung cancer. Oncotarget 2022;13:393–407. doi: 10.18632/oncotarget.28202
- Tombolan L., Orso F., Guzzardo V. et al. High IGFBP2 expression correlates with tumor severity in pediatric rhabdomyosarcoma. Am J Pathol 2011;179:2611–24. doi: 10.1016/j.ajpath.2011.07.018.
- Kaplieva I.V., Zhukova G.V., Sagatelyan S.A. et al. Features of the content of some components of the vascular endothelial growth factor system in the blood of mature and elderly men with primary and recurrent soft tissue sarcomas. Modern problems of science and education 2022;3:96. (In Russ.).
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