Oncotarget

Research Papers:

MiR-99b-5p expression and response to tyrosine kinase inhibitor treatment in clear cell renal cell carcinoma patients

Magdalena Lukamowicz-Rajska _, Christiane Mittmann, Michael Prummer, Qing Zhong, Jens Bedke, Jörg Hennenlotter, Arnulf Stenzl, Axel Mischo, Svenja Bihr, Manuela Schmidinger, Ursula Vogl, Iris Blume, Christoph Karlo, Peter Schraml and Holger Moch

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Oncotarget. 2016; 7:78433-78447. https://doi.org/10.18632/oncotarget.12618

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Abstract

Magdalena Lukamowicz-Rajska1, Christiane Mittmann1, Michael Prummer2, Qing Zhong1, Jens Bedke3, Jörg Hennenlotter3, Arnulf Stenzl3 , Axel Mischo4, Svenja Bihr4, Manuela Schmidinger5, Ursula Vogl5, Iris Blume6, Christoph Karlo6, Peter Schraml1 and Holger Moch1

1 Institute of Surgical Pathology, University Hospital Zürich, Zurich, Switzerland

2 NEXUS Personalized Health Technologies, ETH Zürich, Zürich, Switzerland

3 Department of Urology, University Tübingen, Tübingen, Germany

4 Oncology Department, University Hospital Zürich, Zürich, Switzerland

5 Department of Internal Medicine I, Division of Oncology & Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria

6 Institute for diagnostic and interventional Radiology, University Hospital Zurich, Zürich, Switzerland

Correspondence to:

Magdalena Lukamowicz-Rajska, email:

Keywords: renal cancer, ccRCC, miR, sunitinib, treatment response, microRNA, tyrosine kinase inhibitors

Received: July 14, 2016 Accepted: September 18, 2016 Published: October 12, 2016

Abstract

A number of treatments targeting VEGF or mTOR pathways have been approved for metastatic clear cell Renal Cell Carcinoma (ccRCC), but the majority of patients show disease progression after first line therapy with a very low rate of complete or long-term responders. It has been shown that miRs may play a role in prediction of treatment response in various cancer types. The aim of our study was to identify a miR signature predictive for RCC patients’ response to antiangiogenic tyrosine kinase inhibitor (TKI) treatment in the first line therapy. Sequencing of 40 paired normal/tumor formalin fixed and paraffin embedded ccRCC tissues revealed separate clustering via unsupervised dendrograms. With supervised analysis, the strongest differential expression was obtained with miR-99b-5p, which was significantly lower in patients with short progression free survival (<8 months) and TKI non-responders (progressive disease patients according to RECIST) (p<0.0001, each). Validation using RTqPCR and a second patient cohort compiled from three different hospitals (n=65) showed higher expression of miR-99b-5p in complete responders, but this trend did not reach statistical significance. It is concluded that low miR-99b-5p expression analyzed with sequencing methodology may correlate with tumor progression in TKI-treated ccRCC patients.


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