To identify miRNA characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer specific survival in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue.
RNA was isolated from nephrectomy and kidney biopsy specimens (n=156; n=46 respectively). Samples were grouped: benign, non-progressive and progressive ccRCC. MiRNA were profiled by microarray and validated by qRT-PCR. Biomarker signatures were developed to predict cancer status in nephrectomy and biopsy specimens. Cancer specific survival was examined using Kaplan-Meier and Cox proportional hazards analyses.
Microarray analysis revealed 20 differentially expressed miRNA comparing non-progressive with progressive tumors. A biomarker signature validated in nephrectomy specimens had a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and ccRCC. A second signature differentiated non-progressive versus progressive ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b-5p, and -223-3p were associated with cancer specific survival.
This study identified miRNA differentially expressed in ccRCC samples; as well as those correlating with cancer specific survival. Biomarkers identified in this study have the potential to identify patients who are likely to have progressive ccRCC, and although preliminary, these results may aid in differentiating aggressive and indolent ccRCC based on biopsy specimens. This article is protected by copyright. All rights reserved.
BJU international. 2017 Apr 22 [Epub ahead of print]
Casey G Kowalik, Drew A Palmer, Travis B Sullivan, Patrick A Teebagy, John M Dugan, John A Libertino, Eric J Burks, David Canes, Kimberly M Rieger-Christ
Department of Urology, Lahey Hospital & Medical Center, 41 Mall Road, Burlington, MA, 01805., Department of Translational Research - Ian C. Summerhayes Cell and Molecular Biology Laboratory, Lahey Hospital & Medical Center, 41 Mall Road, Burlington, MA, 01805., Department of Pathology, Lahey Hospital & Medical Center, 41 Mall Road, Burlington, MA, 01805.