Gender differences in components of insulin-like signaling pathway in kidney tissues in local and advanced clear cell renal cell carcinoma

Objective: study of components of an insulin-like signaling pathway in kidney tissues in local and advanced clear cell renal cell carcinoma depending on the gender of patients. Materials and methods: the object of the study was conditionally intact kidney tissue and tumor and perifocal tissues obtained during the surgical treatment of 100 patients with histologically confirmed clear cell kidney cancer (local cancer (Т1-2N0М0) n=50, advanced cancer (Т3-4N0М1) n=50). Levels of the IGF-1, IGF-2, IGFBP-1 and IGFBP-2 growth factors (Mediagnost, Germany) and STH-releasing (Peninsula Laboratories International, USA) were determined by ELISA using standard test systems. The results were analyzed using Statistica 6.0 (Stat-Soft, 2001). Results: levels of IGFВР-2 and STH-releasing in conditionally intact tissues in women were 44% and 40% lower than in men, respectively. The IGFВР-2 level in perifocal tissues of women was 38% higher than in men, while STH-releasing was lower by 1.9 times. Tumor tissues of local kidney cancer in women showed significant decrease in IGF-1 by 25%, IGFВР-1 by 29% and IGFВР-2 by 2 times. Levels of IGFBP-1 and IGFBP-2 in conditionally intact tissues of women with advanced cancer were 2 and 2.7 times lower, respectively, compared to men. IGFBP-2 and STH-releasing in perifocal tissues of women were increased by 43.8% and 44.6%, respectively. In tumor tissues of women with advanced kidney cancer, levels of IGF-1 were 1.7 times higher, IGF-2 – 31% lower, IGFBP-2 – 2.8 times lower and STH-releasing – 36% lower, compared to men. Conclusions: IGFBP-2 in all studied kidney tissues in local and advanced cancer was an identically variable index characterizing gender differences in the body’s reaction to the tumor process.

1. Nasibullin IM, Pavlov VN, Safi ullin RI, Mustafi n AT. Optimization of organ preserving surgery for renal cell carcinoma using xenocollagen adsorbed interferon. Meditsinskii vestnik Bashkortostana. 2006;1(1):97-99. (In Russ)

2. Pronin VS, Koloda DE, Chaplygina EV. Clinical use of insulinlike growth factors: their biological action and perspectives of application. Klinitsist. 2008;1:18-27. (In Russ)

3. Pavelie J, Matijevic T, Knezevic J. Biological&physiological aspects of action of insulin-like growth factor peptide family. Indian J. med. Res. 2007;125(4):511-522

4. Kostyleva OI, Maslyaev AV, Kryuk YuV, Tuleuova AA, Mamedov UR, et al. Breast cancer and IGF. Rossiiskii bioterapevticheskii zhurnal. 2012;11(1):79-84. (In Russ)

5. Kaladze NN, Ezernitskaya AI, Babak ML. Pituitary-epiphyseal system and growth factors in patients with bronchial asthma during sanatorium-resort rehabilitation. Vestnik fi zioterapii i kurortologii. 2016;1:62-76. (In Russ)

6. Tyrenko VV, Kamilova TA, Odin VI. Treatment with insulin analogues - are we able to estimate the risk of cancer? Vestnik Rossiiskoi voenno-meditsinskoi akademii. 2010;29(1):222-229. (In Russ)

7. Gershtein ES, Kushlinskii DN, Korotkova EA, Isaeva ER, Ermilova VD, et al.. Clinical implications of insulin-like growth factors (IGF) and IGF-binding proteins investigation in patients with ovarian neoplasms. Al’manakh klinicheskoi meditsiny. 2015;41:19-27. (In Russ)

8. Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, et al. Th e role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008;114(1):23-37. doi:10.1080/13813450801969715

9. Aksel’ EM. Incidence of malignant neoplasms of urinary and male genital organs in Russia in 2003. Onkourologiya. 2005;1:6-9. (In Russ)

10. Tyuzikov IA, Kalinchenko SYu, Vorslov LO, Grekov EA. Role of insulin resistance in kidney diseases pathogenesis. Eksperimental’naya i klinicheskaya urologiya. 2012;4:23-28. (In Russ)

11. Alyaev YuG, Grigoryan VA, Krapivin AA, Sultanova EA. Kidney tumor. Moscow: GEOTAR-Media; 2002. (In Russ)

12. Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002;23(6):824- 54

13. Hur H, Yu EJ, Ham IH, Jin HJ, Lee D. Preoperative serum levels of insulin-like growth factor-binding protein 2 predict prognosis of gastric cancer patients. Oncotarget. 2017;8(7):10994-11003. doi: 10.18632/oncotarget.14202

14. Bochkareva N.V., Kondakova I.V., Kolomiets L.A., Muntyan A.V. Th e system of insulin-like growth factors in pathogenesis and prognosis of epithelialovarian cancer. Sibirskiy oncologicheskiy zhurnal. 2011;3:74-81. (in Russ.)

15. Nedich O, Masnikoza R. Altered interaction of isolated insulin/IGF receptors as compared to membrane-bound receptors. Biokhimiya. 2009;74(1):39-46. (In Russ)

16. Bach LA. Th e insulin-like growth factor system in kidney disease and hypertension. Curr Opin Nephrol Hypertens. 2012;21(1):86-91. doi: 10.1097/MNH.0b013e32834dc1a2

17. Gershtein ES, Isaeva ER, Ognerubov NA. Insulinlike growth factor system components as prognostic factors and targets for molecular specifi c therapy in ovarian cancer. Vestnik TGU. 2014;19(1):42-46. (in Russ.)

18. Yakar S, Leroith D, Brodt P. Th e role of the growth hormone/ insulin like growth factor axis in tumor growth and progression: Lessons from animal models. Cytokine Growth Factor Rev. 2005;16:407-420. DOI: 10.1016/j.cytogfr.2005.01.010