Prognostic value of matrix metalloproteinases and transforming growth factor – β in kidney cancer
https://doi.org/10.17709/2410-1893-2022-9-2-8
Abstract
Purpose of the study. The study's objective is to investigate the expression level of tissue and serum markers of oncogenesis and nephrofibrosis transforming growth factor beta (TGF‑β) and matrix metalloproteinase‑9 (MMP‑9) in patients operated for various stages of renal cell carcinoma.
Materials and methods. The study prospectively included medical data of 60 patients with kidney cancer with T1–3N0M0 who received surgical treatment in the Clinic of Urologynamed after S. R. Mirotvortsev of the State Medical University from 2016 to 2019. The patients were divided into 3 groups: Group 1 included 20 patients who underwent laparoscopic kidney resection; Group 2–20 patients who underwent laparoscopic nephrectomy; Group 3–20 patients who underwent open nephrectomy. The control group consisted of 15 healthy volunteers without chronic kidney diseases. All patients signed an informed consent to participate in the study. All patients at the preoperative stage, in the early (7–10 days) and remote postoperative periods (after 1 and 2 years) were tested by solid‑phase ELISA on a StatFax 4200 analyzer using eBiosence and Cloud‑Clone Corp reagent kits for the serum concentration of oncogenesis markers MMP‑9 and TGF‑β1.
Results. Initial increase of MMP‑9 concentration was detected in all groups of PCC patients compared to the control group (p ≤ 0.05). According to the results of ROC analysis, this indicator has high specificity and sensitivity for prognosis of preoperative stage of renal cell carcinoma. The sensitivity and specificity of MMP‑9 were 87.5 % and 62 %, respectively, and the diagnostically significant level of MMP‑9 was 958 ng/ml. A comprehensive analysis of the content of MMP‑9 and TGF‑β1 oncogenesis markers in serum and tumor cells revealed the correlation of these indicators in various biological objects.
Conclusion. Markers of oncogenesis and nephrofibrosis TGF‑β1 and MMP‑9 provide an opportunity for non‑invasive monitoring of tumor progression and probability of metastasis in the clinical setting. Serum MMP‑9 are a reliable predictor of tumor growth. Serum TGF‑β1 concentration isn't a sufficiently reliable marker of tumor progression.
About the Authors
A. I. TarasenkoRussian Federation
Artem I. Tarasenko – Cand. Sci. (Med.), deputy director for innovative development of the Institute of Urology and Reproductive Health. SPIN: 7456-4963, AuthorID: 715646, Scopus Author ID: 57199647114
Moscow
A. N. Rossolovskiy
Russian Federation
Anton N. Rossolovskiy – Dr. Sci. (Med.), deputy director, associate professor of the department of urology of the Research Institute of Fundamental and Clinical Uronephrology. SPIN: 4622-7095, AuthorID: 665930, ResearcherID: AAD-4866-2021, Scopus Author ID: 57203353149
8/2 Trubetskaya str., Moscow 119991
O. L. Berezinets
Russian Federation
Oksana L. Berezinets – Cand. Sci. (Med.), senior research fellow at the Research Institute of Fundamental and Clinical Uronephrology. SPIN: 9793-7772, AuthorID: 759235, ResearcherID: AAD-4898-2021, Scopus Author ID: 36665823100
Saratov
A. B. Bucharskaya
Russian Federation
Alla B. Bucharskaya – Cand. Sci. (Biol.), senior research fellow at the Research Institute of Fundamental and Clinical Uronephrology. Scopus Author ID: 11738772400
Saratov
S. S. Pakhomiy
Russian Federation
Svetlana S. Pakhomiy – Cand. Sci. (Med.), associate professor at the department of pathological anatomy. Scopus Author ID: 56048180800
Saratov
A. O. Efimova
Russian Federation
Alena O. Efimova – Cand. Sci. (Med.), dermatovenerologist. SPIN: 6877-0056, AuthorID: 1039569
Moscow
G. N. Maslyakova
Russian Federation
Galina N. Maslyakova – Dr. Sci. (Med.), senior research fellow. Scopus Author ID: 8960549800
Saratov
References
1. Evsyukova ОI, Matveev VВ. Renal cell carcinoma: what’s new in 2019. Cancer Urology. 2019;15(4):120‑125. (In Russ.). https://doi.org/10.17650/1726‑9776‑2019‑15‑4‑120‑125
2. Kazarcev AV, Cherdanceva TM, Bobrov IP, Lazarev AF, Klimachev VV. Intratumoral stromal mast cells in renal cell carcinoma: clinical and morphological comparisons. Russian Journal of Oncology. 2017;22(1):21–24. https://doi.org/10.18821/1028‑9984‑2017‑22‑1‑21‑24
3. Gómez‑Gil V. Therapeutic Implications of TGFβ in Cancer Treatment: A Systematic Review. Cancers (Basel). 2021 Jan 20;13(3):379. https://doi.org/10.3390/cancers13030379
4. Isaka Y. Targeting TGF‑β Signaling in Kidney Fibrosis. Int J Mol Sci. 2018 Aug 27;19(9):2532. https://doi.org/10.3390/ijms19092532
5. Angioni R, Sánchez‑Rodríguez R, Viola A, Molon B. TGF‑β in Cancer: Metabolic Driver of the Tolerogenic Crosstalk in the Tumor Microenvironment. Cancers (Basel). 2021 Jan 22;13(3):401. https://doi.org/10.3390/cancers13030401
6. Gong L, Wu D, Zou J, Chen J, Chen L, Chen Y, et al. Prognostic impact of serum and tissue MMP‑9 in non‑small cell lung cancer: a systematic review and meta‑analysis. Oncotarget. 2016 Apr 5;7(14):18458–18468. https://doi.org/10.18632/oncotarget.7607
7. Vandooren J, Van den Steen PE, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase‑9 (MMP‑9): the next decade. Crit Rev Biochem Mol Biol. 2013 Jun;48(3):222–272. https://doi.org/10.3109/10409238.2013.770819
8. Shi M, Cao M, Song J, Liu Q, Li H, Meng F, et al. PinX1 inhibits the invasion and metastasis of human breast cancer via suppressing NF‑κB/MMP‑9 signaling pathway. Mol Cancer. 2015 Mar 26;14:66. https://doi.org/10.1186/s12943‑015‑0332‑2
9. Bieniaś B, Sikora P. Selected Metal Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases as Potential Biomarkers for Tubulointerstitial Fibrosis in Children with Unilateral Hydronephrosis. Dis Markers. 2020;2020:9520309. https://doi.org/10.1155/2020/9520309
10. Wu D, Pan H, Zhou Y, Zhou J, Fan Y, Qu P. microRNA‑133b downregulation and inhibition of cell proliferation, migration and invasion by targeting matrix metallopeptidase‑9 in renal cell carcinoma. Mol Med Rep. 2014 Jun;9(6):2491–2498. https://doi.org/10.3892/mmr.2014.2116
11. Kallakury BV, Karikehalli S, Haholu A, Sheehan CE, Azumi N, Ross JS. Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma. Clin Cancer Res. 2001 Oct;7(10):3113–3119.
12. Cherdantseva TM, Bobrov IP, Varlamov SV, Myadelets MN, Klimachev IV, Avdalyan AM, et al. Prognostic value of matrix metalloproteinase 9 in renal cell carcinoma. Cancer Urology. 2018;14(3):17–24. (In Russ.). https://doi.org/10.17650/1726‑9776‑2018‑14‑3‑17‑24
13. Ning J, Zhao Y, Ye Y, Yu J. Opposing roles and potential antagonistic mechanism between TGF‑β and BMP pathways: Implications for cancer progression. EBioMedicine. 2019 Mar;41:702–710. https://doi.org/10.1016/j.ebiom.2019.02.033
14. Gómez‑Gil V. Therapeutic Implications of TGFβ in Cancer Treatment: A Systematic Review. Cancers (Basel). 2021 Jan 20;13(3):379. https://doi.org/10.3390/cancers13030379
Supplementary files
Review
For citations:
Tarasenko A.I., Rossolovskiy A.N., Berezinets O.L., Bucharskaya A.B., Pakhomiy S.S., Efimova A.O., Maslyakova G.N. Prognostic value of matrix metalloproteinases and transforming growth factor – β in kidney cancer. Research and Practical Medicine Journal. 2022;9(2):96-106. (In Russ.) https://doi.org/10.17709/2410-1893-2022-9-2-8