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Br J Cancer. 2015 Nov 3;113(9):1313-22. doi: 10.1038/bjc.2015.352. Epub 2015 Oct 13.

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.

Author information

1
Inserm, UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, IUH, rue Juliette Dodu 27, F-75010 Paris, France.
2
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, rue de l'Ecole de Médecine 15, F-75006 Paris, France.
3
Department of General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium.
4
Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre le Cancer, rue Corvisart 14, F-75013 Paris, France.
5
Department of Medical Oncology, Hôpital Foch, rue Worth 40, F-92150 Suresnes, France.
6
Department of Medical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte-Marguerite, F-13273 Marseille, France.
7
Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Avenue du Maréchal de Lattre de Tassigny 51, F-94000 Créteil, France.
8
Department of Medical Oncology, Institut Gustave Roussy, rue Edouard Vaillant 114, F-94800 Villejuif, France.
9
Department of Urology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium.
10
Department of Pathology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, rue de Sèvres 149, F-75015 Paris, France.
11
Department of Pathology, University Hospitals Leuven, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium.
12
Department of Urology, Hôpital Bicêtre, rue du Général Leclerc 78, F-94270 Le Kremlin-Bicêtre, France.
13
Department of Urology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Rue Leblanc 20, F-75015 Paris, France.
14
Department of Medical Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Rue Leblanc 20, F-75015 Paris, France.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

PMID:
26528707
PMCID:
PMC4815796
DOI:
10.1038/bjc.2015.352
[Indexed for MEDLINE]
Free PMC Article

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