Long non-coding RNAs (lncRNAs) serve an important role in cancer progression and may be used as efficient molecular biomarkers. The present study aimed to identify lncRNAs associated with the response to the receptor tyrosine kinase inhibitor sunitinib and transcriptome profile and clinical features of metastatic renal cell carcinoma (mRCC). The gene expression of 84 cancer-associated lncRNAs in tumor and non-malignant tissue samples of 38 patients with mRCC was evaluated using quantitative PCR. In addition, the coding transcriptome was estimated using RNA sequencing in a subgroup of 20 patients and mRNA-lncRNA intersections were identified. In total, 37 and 13 lncRNAs were down- and upregulated, respectively, in tumor compared with non-malignant adjacent tissue samples. A total of 10 and 4 lncRNAs were up- and downregulated, respectively, in good responders to sunitinib compared with poor responders. High expression of HNF1A-AS1 and IPW lncRNAs was associated with prolonged progression-free survival of patients and a high expression of the TUSC7 lncRNA was associated with poor response and worse survival. Significant associations of dysregulated MEG3 and SNHG16 lncRNAs with expression of protein-coding genes representing various pathways, were identified. Furthermore, a significantly higher expression of CLIP4 gene was observed in good responders. The present study revealed promising candidates for predictive and prognostic biomarkers with further therapeutic potential.

Department of Oncology and Radiotherapeutics Faculty of Medicine in Pilsen and University Hospital Charles University 323 00 Pilsen Czech Republic

Department of Pathology Faculty of Medicine in Pilsen and University Hospital Charles University 301 00 Pilsen Czech Republic

Department of Urology Faculty of Medicine in Pilsen and University Hospital Charles University 301 00 Pilsen Czech Republic

Laboratory of Cancer Treatment and Tissue Regeneration Biomedical Center Faculty of Medicine in Pilsen Charles University 323 00 Pilsen Czech Republic

Laboratory of Pharmacogenomics Biomedical Center Faculty of Medicine in Pilsen Charles University 323 00 Pilsen Czech Republic

Toxicogenomics Unit National Institute of Public Health 100 00 Prague 10 Czech Republic

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