Theranostics 2018; 8(9):2447-2458. doi:10.7150/thno.23002

Research Paper

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

Maeva Dufies1, Marie Nollet2, Damien Ambrosetti3, Wael Traboulsi2, Julien Viotti4, Delphine Borchiellini5, Renaud Grépin1, Julien Parola6, Sandy Giuliano1, Dominique Helley-Russick7, Karim Bensalah8, Alain Ravaud9, Jean-Christophe Bernhard10, Renaud Schiappa4, Nathalie Bardin2, Françoise Dignat-George2, Nathalie Rioux-Leclercq11, Stephane Oudard7, Sylvie Négrier12, Jean-Marc Ferrero5, Emmanuel Chamorey4, Marcel Blot-Chabaud2*, Gilles Pagès6✉*

1. Centre Scientifique de Monaco, Biomedical Department, 8 Quai Antoine Ier, MC-98000 Monaco, Principality of Monaco.
2. Aix Marseille Univ, INSERM 1263, INRA 1260, C2VN, Marseille, France.
3. University Cote d'Azur, Nice University Hospital, Department of Pathology,
4. Centre Antoine Lacassagne, Statistic department, Nice, France
5. Centre Antoine Lacassagne, Clinical research department Nice, France
6. University Cote d'Azur, Institute for research on cancer and aging of Nice, CNRS UMR 7284; INSERM U1081, Centre Antoine Lacassagne, France.
7. European Hospital Georges Pompidou, Paris, France
8. Centre Hospitalier Universitaire (CHU) de Pontchaillou Rennes, service d'urologie
9. Bordeaux University, Bordeaux University Hospital (CHU), Medical Oncology department, Bordeaux, France.
10. Bordeaux University, Bordeaux University Hospital (CHU), Urology department, Bordeaux, France.
11. Rennes University, Rennes University Hospital, Department of Pathology, Rennes, France
12. Centre Léon Bérard, Lyon, France
*MBC and GP co-directed the work

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Citation:
Dufies M, Nollet M, Ambrosetti D, Traboulsi W, Viotti J, Borchiellini D, Grépin R, Parola J, Giuliano S, Helley-Russick D, Bensalah K, Ravaud A, Bernhard JC, Schiappa R, Bardin N, Dignat-George F, Rioux-Leclercq N, Oudard S, Négrier S, Ferrero JM, Chamorey E, Blot-Chabaud M, Pagès G. Soluble CD146 is a predictive marker of pejorative evolution and of sunitinib efficacy in clear cell renal cell carcinoma. Theranostics 2018; 8(9):2447-2458. doi:10.7150/thno.23002. Available from https://www.thno.org/v08p2447.htm

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Abstract

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: sCD146, clear cell renal cell carcinoma, sunitinib, predictive marker, plasma