Supplemental Table 1-3 from Molecular Subtypes of Clear Cell Renal Cell Carcinoma Are Associated with Sunitinib Response in the Metastatic Setting

Beuselinck, Benoit; Job, Sylvie; Becht, Etienne; Karadimou, Alexandra; Verkarre, Virginie; Couchy, Gabrielle; Giraldo, Nicolas; Rioux-Leclercq, Nathalie; Molinié, Vincent; Sibony, Mathilde; Elaidi, Reza; Teghom, Corinne; Patard, Jean-Jacques; Méjean, Arnaud; Fridman, Wolf Herman; Sautès-Fridman, Catherine; de Reyniès, Aurélien; Oudard, Stéphane; Zucman-Rossi, Jessica

doi:10.1158/1078-0432.22459037.v1

Supplemental Table 1-3 from Molecular Subtypes of Clear Cell Renal Cell Carcinoma Are Associated with Sunitinib Response in the Metastatic Setting

journal contribution

posted on 2023-03-31, 18:47 authored by Benoit Beuselinck, Sylvie Job, Etienne Becht, Alexandra Karadimou, Virginie Verkarre, Gabrielle Couchy, Nicolas Giraldo, Nathalie Rioux-Leclercq, Vincent Molinié, Mathilde Sibony, Reza Elaidi, Corinne Teghom, Jean-Jacques Patard, Arnaud Méjean, Wolf Herman Fridman, Catherine Sautès-Fridman, Aurélien de Reyniès, Stéphane Oudard, Jessica Zucman-Rossi

Supplemental Table 1-3. Table S1: Clinical and pathological characteristics of patients. Table S2: List of the 70 genes used for quantitative Real-Time PCR, their Applied Biosystems Assay ID number and the subgroups in which the genes are up- or down-regulated in the Affymetrix data. Table S3: (A) Diagram showing the different analyses that have been done on the samples and (B) sample list according to the different technologies.

History

ARTICLE ABSTRACT

Purpose: Selecting patients with metastatic clear-cell renal cell carcinoma (m-ccRCC) who might benefit from treatment with targeted tyrosine kinase inhibitors (TKI) is a challenge. Our aim was to identify molecular markers associated with outcome in patients with m-ccRCC treated with sunitinib.Experimental Design: We performed global transcriptome analyses on 53 primary resected ccRCC tumors from patients who developed metastatic disease and were treated with first-line sunitinib. We also determined chromosome copy-number aberrations, methylation status, and gene mutations in von Hippel–Lindau and PBRM1. Molecular data were analyzed in relation with response rate (RR), progression-free survival (PFS), and overall survival (OS). Validation was performed in 47 additional ccRCC samples treated in first-line metastatic setting with sunitinib.Results: Unsupervised transcriptome analysis identified 4 robust ccRCC subtypes (ccrcc1 to 4) related to previous molecular classifications that were associated with different responses to sunitinib treatment. ccrcc1/ccrcc4 tumors had a lower RR (P = 0.005) and a shorter PFS and OS than ccrcc2/ccrcc3 tumors (P = 0.001 and 0.0003, respectively). These subtypes were the only significant covariate in the multivariate Cox model for PFS and OS (P = 0.017 and 0.006, respectively). ccrcc1/ccrcc4 tumors were characterized by a stem-cell polycomb signature and CpG hypermethylation, whereas ccrcc3 tumors, sensitive to sunitinib, did not exhibit cellular response to hypoxia. Moreover, ccrcc4 tumors exhibited sarcomatoid differentiation with a strong inflammatory, Th1-oriented but suppressive immune microenvironment, with high expression of PDCD1 (PD-1) and its ligands.Conclusions: ccRCC molecular subtypes are predictive of sunitinib response in metastatic patients, and could be used for personalized mRCC treatment with TKIs, demethylating or immunomodulatory drugs. Clin Cancer Res; 21(6); 1329–39. ©2015 AACR.