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

• DOI: 10.18632/oncotarget.12618
• Publication Date: 2016-10-13T05:27:08Z
• Authors: Magdalena Lukamow...; 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; Holger Moch
• Keywords: Tumor progression

// Magdalena Lukamowicz-Rajska 1 , Christiane Mittmann Michael Prummer 2 Qing Zhong Jens Bedke 3 Jörg Hennenlotter Arnulf Stenzl Axel Mischo 4 Svenja Bihr Manuela Schmidinger 5 Ursula Vogl Iris Blume 6 Christoph Karlo Peter Schraml and Holger Moch Institute of Surgical Pathology, University Hospital Zürich, Zurich, Switzerland NEXUS Personalized Health Technologies, ETH Department Urology, Tübingen, Germany Oncology Department, Internal Medicine I, Division & Comprehensive Cancer Center Vienna, Medical Austria for diagnostic interventional Radiology, Correspondence to: Lukamowicz-Rajska, email: Keywords : renal cancer, ccRCC, miR, sunitinib, treatment response, microRNA, tyrosine kinase inhibitors Received July 14, 2016 Accepted September 18, Published October 12, Abstract A number treatments targeting VEGF or mTOR pathways have been approved metastatic clear cell Renal Cell Carcinoma (ccRCC), but the majority patients show disease progression after first line therapy with a very low rate complete long-term responders. It has shown that miRs may play role in prediction response various cancer types. The aim our study was to identify miR signature predictive RCC patients' antiangiogenic inhibitor (TKI) therapy. Sequencing 40 paired normal/tumor formalin fixed paraffin embedded ccRCC tissues revealed separate clustering via unsupervised dendrograms. With supervised analysis, strongest differential expression obtained miR-99b-5p, which significantly lower short free survival (<8 months) TKI non-responders (progressive according RECIST) (p<0.0001, each). Validation using RTqPCR second patient cohort compiled from three different hospitals (n=65) showed higher miR-99b-5p responders, this trend did not reach statistical significance. is concluded analyzed sequencing methodology correlate tumor TKI-treated patients.