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- Title
RANK/OPG ratio of expression in primary clear-cell renal cell carcinoma is associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs.
- Authors
Beuselinck, B; Jean-Baptiste, J; Couchy, G; Job, S; De Reynies, A; Wolter, P; Théodore, C; Gravis, G; Rousseau, B; Albiges, L; Joniau, S; Verkarre, V; Lerut, E; Patard, J J; Schöffski, P; Méjean, A; Elaidi, R; Oudard, S; Zucman-Rossi, J; Théodore, C
- Abstract
<bold>Background: </bold>Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs.<bold>Methods: </bold>Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression.<bold>Results: </bold>We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001).<bold>Conclusions: </bold>RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.
- Subjects
PROTEIN kinase inhibitors; BONE tumors; CELL receptors; CELLULAR signal transduction; GROWTH factors; KIDNEY tumors; MEMBRANE proteins; ONCOGENES; PROGNOSIS; PROTEIN-tyrosine kinases; RENAL cell carcinoma; TUMOR necrosis factors; CHEMICAL inhibitors; THERAPEUTICS
- Publication
British Journal of Cancer, 2015, Vol 113, Issue 9, p1313
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/bjc.2015.352