online ISSN 2415-3176
print ISSN 1609-6371
logoExperimental and Clinical Physiology and Biochemistry
  • 8 of 10
ECPB 2017, 77(1): 49–53
Research articles

The Possibility of Application of Detected in Urine MicroRNA-15a for Diagnostics of Renal Cell Carcinoma


Renal cell carcinoma (RCC) is the most common primary renal tumor, 5-year survival of patients with RCC rates of 35 %. According to various data the part of non-diagnostic percutaneous puncture kidney biopsies is high and varies from 5 to 40 %. In RCC diagnostics application of contemporary imaging methods such as CT or MRI doesn’t guarantee 100 % sensitivity and specificity and it ranges from 88 to 96 %. At the moment the role of miRNAs in malignant tumors pathogenesis and the possibility to use them as cancer biomarkers is actively investigated. The aim. The aim of the study was to assess the possibility of miRNA-15a application as a molecular diagnostic biomarker of RCC by measuring its expression in urine. Material and methods. The study enrolled 34 patients with primary RCC. The size of the tumor ranged from 3.5 to 11.4 cm, with median size of 7.2 ± 5.3 cm in the greatest dimension. Surgery was performed in all patients. The main group included patients with pathologically confirmed RCC. A day before surgery a morning urine in volume 100-150 ml was gathered into sterile container in all patients, all samples were cryopreserved at -25 °С. For the reference urine was also obtained and preserved in the same way from 30 healthy volunteers without renal pathology. Isolation of the miR-15а from the urine was performed in patients of the main and control groups followed by determination of its expression by using a reverse transcription and real time polymerase chain reaction.

Results. As a result of the study we observed statistically significant difference (р < 0.05) in the levels of miR-15a expression between the main and control groups: in patients with RCC the mean value was 47.39 ± 24.63 RFU (range - 0,42-99,34 RFU) against 0,04 ± 0,02 RFU (range - 0,01-0,05 RFU) in healthy volunteers. Static analysis didn’t discover in patients with RCC the correlation between size and level of miR-15a expression of the tumor and it was r = 0.35, simultaneously data about tumor-protective role of miRNA-15а that we obtained discords with data of other researchers.

Conclusions. As a result of our study we observed statistically significant difference (р < 0.05) between the mean levels of miR-15a expression in the urine of the patients with RCC and healthy persons. MiR-15a, which was found in urine, may be used as a molecular biomarker of RCC for diagnostics and screening of this disease. The advantage of this diagnostic method is its noninvasiveness and the disadvantage is a necessity in cryopreservation at -25 °С till microRNA isolation. Further investigations with inclusion of larger number of patients with different histological sybtypes of RCC of different grades, benign tumors of kidneys for deeper analysis of the diagnostic value of miR-15a required.

Added 30.01.2017

Keywords: renal cell carcinoma, biomarker, microRNA-15a, diagnostics

Full text: PDF (Ukr) 0.99M

  1. 1. Stroy O, Banyra O, Shuliak O. The value of miR-508-3р in kidney cancer diagnostics. Ukraisnky Medychny Chasopys. 2012;2:1-3.
  2. 2. Alderman C, Sehlaoui A, Xiao Z, Yang Y. MicroRNA-15a inhibits the Growth and Invasiveness of Malignant Melanoma and Directly Targets on CDCA4 Gene. Tumour Biology. 2016;4:1-6.
  3. 3. Blute M, Prince J, Bultman E, Hinshaw L, Drewry A, Best S et al. Predictors of non-diagnostic renal mass biopsy. The Journal of Urology. 2015;4(193):532-533.
  4. 4. Brandenstein M, Pandarakalam J, Kroon L, Loeser H, Herden J, Braun G et al. MicroRNA 15a, Inversely Correlated to PKCα, Is a Potential Marker to Differentiate between Benign and Malignant Renal Tumors in Biopsy and Urine Samples. The American Journal of Pathology. 2012;5(180):1787-97.
  5. 5. Chen X, Wang X, Ruan A, Han W, Zhao Y, Lu X et al. MiR-141 is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression. Clinical Cancer Research. 2014;10(20):2617-30.
  6. 6. Fujii Y, Komai Y, Saito K, Iimura Y, Yonese J, Kawakami S et al. Incidence of Benign Pathologic Lesions at Nephrectomy for Renal Masses Presumed to Be Stage I Renal Cell Carcinoma in Japanese Patients: Impact of Sex, Age, and Tumor Size. ASCO Meeting Abstracts. 2011;7(29):374.
  7. 7. Gao Shen-Meng, Chong-Yun Xing, Chi-Qi Chen, Si-si Lin, Pei-hong Dong, and Fu-jun Yu. MiR-15a and miR-16-1 inhibit the Proliferation of Leukemic Cells by down-Regulating WT1 Protein Level. Journal of Experimental & Clinical Cancer Research. 2011;30:110.
  8. 8. Iwamoto Hideto, Kanda Yusuke, Sejima Takehiro, Osaki Mitsuhiko, Okada Futoshi, Takenaka Atsushi. Serum miR-210 as a Potential Biomarker of Early Clear Cell Renal Cell Carcinoma. International Journal of Oncology. 2014;1(44):53-58.
  9. 9. Kim See Hyung, Kim Chan Sun, Kim Mi Jeong, Cho Jeong Yeon, Cho Seung Hyun. Differentiation of Clear Cell Renal Cell Carcinoma From Other Subtypes and Fat-Poor Angiomyolipoma by Use of Quantitative Enhancement Measurement During Three-Phase MDCT. American Journal of Roentgenology. 2016;1(206):21-28.
  10. 10. Menogue S, O'Brien B, Brown A. Cohen RJ. Percutaneous Core Biopsy of Small Renal Mass Lesions: A Diagnostic Tool to Better Stratify Patients for Surgical Intervention. BJU International. 2013;4(111):146-151.
  11. 11. Pierorazio Phillip M, Michael H. Management of Renal Masses and Localized Renal Cancer: Systematic Review and Meta-Analysis. The Journal of Urology. 2016;196(4):989-99.
  12. 12. Shinden Y, Akiyoshi S, Ueo H, Nambara S, Saito T, Komatsu H et al. Diminished Expression of MiR-15a Is an Independent Prognostic Marker for Breast Cancer Cases. Anticancer Research. 2015;1(35):123-27.
  13. 13. Spek A, Szabados B, Ziegelmüller B, Stief C, D'Anastasi M, Staehler M. Clinical Usage of Different Guidelines in Routine Management, Therapy and Follow-Up of Patients with Renal Cell Cancer in Germany. Urologia Internationalis. 2016;1:1-5.
  14. 14. Teixeira Ana L., Ferreira Marta, Silva Joana. Higher Circulating Expression Levels of miR-221 Associated with Poor Overall Survival in Renal Cell Carcinoma Patients. Tumour Biology. 2014;5(35):4057-66.
  15. 15. Erika Terzuoli, Sandra Donnini, Federica Finetti, Gabriella Nesi, Donata Villari, Hiromi Hanaka et al. Linking Microsomal Prostaglandin E Synthase-1/PGE-2 Pathway with miR-15a and -186 Expression: Novel Mechanism of VEGF Modulation in Prostate Cancer. Oncotarget. 2016;1:2-6.
  16. 16. Vergho Daniel, Susanne Kneitz, Andreas Rosenwald, Scherer Charlotte, Spahn Martin, Burger Maximilian et al. Daniel Vergho, Susanne Kneitz, Andreas Rosenwald, Hubertus Riedmiller, Burkhard Kneitz Combination of Expression Levels of miR-21 and miR-126 Is Associated with Cancer-Specific Survival in Clear-Cell Renal Cell Carcinoma. BMC Cancer. 2014;14(25):1-10.
  17. 17. Xie T, Liu P, Chen L, Chen Z, Luo Y, Chen X et al. MicroRNA-15a down-regulation is Associated with Adverse Prognosis in Human Glioma. Clinical & Translational Oncology. 2015;7(17):504-10.
  18. 18. Zhang H, Gan Q, Wu Y, Liu R, Liu X, Huang Z et al. Diagnostic Performance of Diffusion-Weighted Magnetic Resonance Imaging in Differentiating Human Renal Lesions (Benignity or Malignancy): A Meta-Analysis. Abdominal Radiology. 2016;10(41):1997-2010.
  19. 19. Zhu K, He Y, Xia C, Yan J, Hou J, Kong D et al. MicroRNA-15a Inhibits Proliferation and Induces Apoptosis in CNE1 Nasopharyngeal Carcinoma Cells. Oncology Research. 2016;3(24):145-51.

Програмування -