Soluble CD146 is a predictive marker of pejorative evolution and of sunitinib efficacy in clear cell renal cell carcinoma

Maeva Dufies (1) , Marie Nollet (2) , Damien Ambrosetti (3) , Wael Traboulsi (2) , Julien Viotti (4) , Delphine Borchiellini (5) , Renaud Grépin (1) , Julien Parola (6) , Sandy Giuliano (1) , Dominique Helley-Russick (7) , Karim Bensalah (8) , Alain Ravaud (9) , Jean-Christophe Bernhard (10, 11) , Renaud Schiappa (5) , Nathalie Bardin (2) , Francoise Dignat-George (2) , Nathalie Rioux-Leclercq (12, 13) , Stéphane Oudard (7) , Sylvie Négrier (14) , Jean-Marc Ferrero (5) , Emmanuel Chamorey (5) , Marcel Blot-Chabaud (2) , Gilles Pagès (5, 6)

1 CSM - Centre Scientifique de Monaco
2 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
3 COMUE UCA - COMUE Université Côte d'Azur (2015-2019)
4 CNRS UMR7284, INSERM U1081, Institute for Research on Cancer and Aging, Nice (IRCAN), Centre Antoine Lacassagne
5 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
6 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
7 Assistance Publique-Hôpitaux de Paris, Hopital Europeen Georges Pompidou, F-75015 Paris, France
8 CHU Pontchaillou [Rennes]
9 Cancérologie/Oncologie/Digestive - Département d'Oncologie [CHU Bordeaux]
10 service d'urologie [CHU Bordeaux]
11 UB - Université de Bordeaux
12 Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes]
13 Irset - Institut de recherche en santé, environnement et travail
14 Centre Léon Bérard [Lyon]

The objective of the study was to use CD146 mRNA to predict the evolution of patients with non-metastatic clear cell renal cell carcinoma (M0 ccRCC) towards metastatic disease, and to use soluble CD146 (sCD146) to anticipate relapses on reference treatments by sunitinib or bevacizumab in patients with metastatic ccRCC (M1). Methods: A retrospective cohort of M0 patients was used to determine the prognostic role of intra-tumor CD146 mRNA. Prospective multi-center trials were used to define plasmatic sCD146 as a predictive marker of sunitinib or bevacizumab efficacy for M1 patients. Results: High tumor levels of CD146 mRNA were linked to shorter disease-free survival (DFS) and overall survival (OS). ccRCC patients from prospective cohorts with plasmatic sCD146 variation <120% following the first cycle of sunitinib treatment had a longer progression-free survival (PFS) and OS. The plasmatic sCD146 variation did not correlate with PFS or OS for the bevacizumab-based treatment. In vitro, resistant cells to sunitinib expressed high levels of CD146 mRNA and protein in comparison to sensitive cells. Moreover, recombinant CD146 protected cells from the sunitinib-dependent decrease of cell viability. Conclusion: CD146/sCD146 produced by tumor cells is a relevant biological marker of ccRCC aggressiveness and relapse on sunitinib treatment.

Keywords: sunitinib; clear cell renal cell carcinoma; sCD146; predictive marker; plasma

Domains: Life Sciences [q-bio]

Maeva Dufies, Marie Nollet, Damien Ambrosetti, Wael Traboulsi, Julien Viotti, et al.. Soluble CD146 is a predictive marker of pejorative evolution and of sunitinib efficacy in clear cell renal cell carcinoma. Theranostics, 2018, 8 (9), pp.2447-2458. ⟨10.7150/thno.23002⟩. ⟨hal-02060593⟩