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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

SCImago Journal Rank (SJR) 2017: 1.114
Source Normalized Impact per Paper (SNIP) 2017: 1.188

Online
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1437-4331
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Volume 56, Issue 9

Issues

MicroRNAs as predictive biomarkers of response to tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma

Julia Kovacova / Alexandr Poprach
  • Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Tomas Buchler
  • Department of Oncology, Thomayer Hospital and Charles University First Faculty of Medicine, Prague, Czech Republic
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ William C. Cho / Ondrej Slaby
  • Corresponding author
  • Central European Institute of Technology, Masaryk University, Brno, Czech Republic
  • Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-02-16 | DOI: https://doi.org/10.1515/cclm-2017-0861

Abstract

Renal cell carcinoma (RCC) accounts for 2%–3% of all malignant tumours. The first-choice treatment in metastatic RCC (mRCC) patients is tyrosine kinase inhibitors (TKIs). Although TKIs may prolong survival of the treated patients who are not primary resistant, almost all of them will eventually develop secondary resistance to the treatment after a progression-free period. To predict treatment response, thus, we need efficient biomarkers for rational indication of TKIs in mRCC. MicroRNAs (miRNAs) not only play important roles in the pathogenesis of many cancers, including RCC but also have been shown to serve as promising diagnostic, prognostic and predictive biomarkers in various cancers. However, the potential of miRNAs to predict response to therapy with TKIs in mRCC has not yet gained sufficient attention. Because personalisation of the TKIs indication in mRCC presents an important unmet medical need, we summarise research on this topic and give an overall insight on the current knowledge in this field.

Keywords: miRNAs; prediction; renal cell carcinoma; sunitinib; tyrosine kinase inhibitor

References

  • 1.

    Le Tourneau C, Raymond E, Faivre S. Sunitinib: a novel tyrosine kinase inhibitor. A brief review of its therapeutic potential in the treatment of renal carcinoma and gastrointestinal stromal tumors [GIST]. Ther Clin Risk Manag 2007;3:341–8.PubMedCrossrefGoogle Scholar

  • 2.

    Bamias A, Escudier B, Sternberg CN, Zagouri F, Dellis A, Djavan B, et al. Current clinical practice guidelines for the treatment of renal cell carcinoma: a systematic review and critical evaluation. Oncologist 2017;22:667–79.Web of SciencePubMedCrossrefGoogle Scholar

  • 3.

    Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol 2009;27:3584–90.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 4.

    Rini BI, Atkins MB. Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol 2009;10:992–1000.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 5.

    Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci USA 2008;105:1516–21.CrossrefGoogle Scholar

  • 6.

    Fasanaro P, D’Alessandra Y, Di Stefano V, Melchionna R, Romani S, Pompilio G, et al. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 2008;283:15878–83.CrossrefWeb of SciencePubMedGoogle Scholar

  • 7.

    Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 2008;15:261–71.CrossrefWeb of SciencePubMedGoogle Scholar

  • 8.

    “MiRBase.” MiRBase. Accessed September 1, 2017. http://www.mirbase.org/index.shtml.

  • 9.

    Youssef YM, White NM, Grigull J, Krizova A, Samy C, Mejia-Guerrero S, et al. Accurate molecular classification of kidney cancer subtypes using microRNA signature. Eur Urol 2011;59:721–30.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 10.

    Khella HW, Butz H, Ding Q, Rotondo F, Evans KR, Kupchak P, et al. miR-221/222 are involved in response to sunitinib treatment in metastatic renal cell carcinoma. Mol Ther 2015;23:1748–58.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 11.

    Leite KR, Canavez JM, Reis ST, Tomiyama AH, Piantino CB, Sañudo A, et al. miRNA analysis of prostate cancer by quantitative real time PCR: comparison between formalin-fixed paraffin embedded and fresh-frozen tissue. Urol Oncol 2011;29:533–7.Web of SciencePubMedCrossrefGoogle Scholar

  • 12.

    Faragalla H, Youssef YM, Scorilas A, Khalil B, White NM, Mejia-Guerrero S, et al. The clinical utility of miR-21 as a diagnostic and prognostic marker for renal cell carcinoma. J Mol Diagn 2012;14:385–92.Web of ScienceCrossrefPubMedGoogle Scholar

  • 13.

    Cho WC. Great potential of miRNAs as predictive and prognostic markers for cancer. Expert Rev Mol Diagn 2012;12:315–8.Web of SciencePubMedCrossrefGoogle Scholar

  • 14.

    Cho WC. MicroRNAs: potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol 2010;42:1273–81.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 15.

    Redova M, Poprach A, Nekvindova J, Iliev R, Radova L, Lakomy R, et al. Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma. J Transl Med 2012;10:55.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 16.

    Zhao A, Li G, Péoc’h M, Genin C, Gigante M. Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol 2013;94:115–20.Web of ScienceCrossrefPubMedGoogle Scholar

  • 17.

    Petillo D, Kort EJ, Anema J, Furge KA, Yang XJ, Teh BT. MicroRNA profiling of human kidney cancer subtypes. Int J Oncol 2009;35:109–14.Web of SciencePubMedGoogle Scholar

  • 18.

    Slaby O, Redova M, Poprach A, Nekvindova J, Iliev R, Radova L, et al. Identification of MicroRNAs associated with early relapse after nephrectomy in renal cell carcinoma patients. Genes Chromosomes Cancer 2012;51:707–16.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 19.

    Silva-Santos RM, Costa-Pinheiro P, Luis A, Antunes L, Lobo F, Oliveira J, et al. MicroRNA profile: a promising ancillary tool for accurate renal cell tumour diagnosis. Br J Cancer 2013;109:2646–53.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 20.

    Slaby O, Jancovicova J, Lakomy R, Svoboda M, Poprach A, Fabian P, et al. Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy. J Exp Clin Cancer Res 2010;29:90.Web of ScienceCrossrefPubMedGoogle Scholar

  • 21.

    Poliseno L, Tuccoli A, Mariani L, Evangelista M, Citti L, Woods K, et al. MicroRNAs modulate the angiogenic properties of HUVECs. Blood 2006;108:3068–71.CrossrefPubMedGoogle Scholar

  • 22.

    Carmeliet P. Angiogenesis in health and disease. Nat Med 2003;9:653–60.CrossrefPubMedGoogle Scholar

  • 23.

    Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9:327–37.PubMedGoogle Scholar

  • 24.

    Würdinger T, Tannous BA, Saydam O, Skog J, Grau S, Soutschek J, et al. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell 2008;14:382–93.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 25.

    Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 2008;132:875–86.PubMedCrossrefGoogle Scholar

  • 26.

    Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T, Chen C-Z, et al. Attribution of vascular phenotypes of the murine Egfl7 locus to the microRNA miR-126. Development 2008;135:3989–93.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 27.

    Fish JE, Santoro MM, Morton SU, Yu S, Yeh R-F, Wythe JD, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 2008;15:272–84.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 28.

    Turchinovich A, Cho WC. The origin, function and diagnostic potential of extracellular microRNA in human body fluids. Front Genet 2014;5:30.PubMedWeb of ScienceGoogle Scholar

  • 29.

    García-Donas J, Beuselinck B, Inglada-Pérez L, Graña O, Schöffski P, Wozniak A, et al. Deep sequencing reveals microRNAs predictive of antiangiogenic drug response. JCI Insight [Internet]. 1. [accessed 2017 Aug 26]. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033860/.

  • 30.

    Berkers J, Govaere O, Wolter P, Beuselinck B, Schöffski P, van Kempen LC, et al. A possible role for microRNA-141 down- regulation in sunitinib resistant metastatic clear cell renal cell carcinoma through induction of epithelial-to-mesenchymal transition and hypoxia resistance. J Urol 2013;189:1930–8.CrossrefWeb of SciencePubMedGoogle Scholar

  • 31.

    Gámez-Pozo A, Antón-Aparicio LM, Bayona C, Borrega P, Gallegos Sancho MI, García-Domínguez R, et al. MicroRNA expression profiling of peripheral blood samples predicts resistance to first-line sunitinib in advanced renal cell carcinoma patients. Neoplasia 2012;14:1144–52.CrossrefWeb of SciencePubMedGoogle Scholar

  • 32.

    Prior C, Perez-Gracia JL, Garcia-Donas J, Rodriguez-Antona C, Guruceaga E, Esteban E, et al. Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma. PLoS One 2014;9:e86263.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 33.

    Merhautova J, Hezova R, Poprach A, Kovarikova A, Radova L, Svoboda M, et al. miR-155 and miR-484 are associated with time to progression in metastatic renal cell carcinoma treated with sunitinib [Internet]. BioMed Res Int 2015 [cited 2017 Aug 26]. Available from: https://www.hindawi.com/journals/bmri/2015/941980/.

  • 34.

    PubMed Help [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2005-. PubMed Help. [Updated 2017 Aug 29]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK3827/.

  • 35.

    Heinzelmann J, Henning B, Sanjmyatav J, Posorski N, Steiner T, Wunderlich H, et al. Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol 2011;29:367–73.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 36.

    White NM, Bao TT, Grigull J, Youssef YM, Girgis A, Diamandis M, et al. miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. J Urol 2011;186: 1077–83.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 37.

    Teixeira AL, Ferreira M, Silva J, Gomes M, Dias F, Santos JI, et al. Higher circulating expression levels of miR-221 associated with poor overall survival in renal cell carcinoma patients. Tumor Biol 2014;35:4057–66.CrossrefWeb of ScienceGoogle Scholar

About the article

Corresponding author: Assoc. Prof. Ondrej Slaby, PhD, Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic


Received: 2017-09-24

Accepted: 2018-01-08

Published Online: 2018-02-16

Published in Print: 2018-08-28


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Supported by the Ministry of Health of the Czech Republic, grant No. 15-34678A. All rights reserved.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 9, Pages 1426–1431, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0861.

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