ONCOmmunity

RAC1b overexpression correlates with poor prognosis in KRAS/BRAF WT metastatic colorectal cancer patients treated with first-line FOLFOX/XELOX chemotherapy.

By: Virginia Alonso-Espinaco, Miriam Cuatrecasas, Vicente Alonso, Pilar Escudero, Maribel Marmol, Carlos Horndler, Javier Ortego, Rosa Gallego, Jordi Codony-Servat, Xabier Garcia-Albeniz, Pedro Jares, Antoni Castells, Juan José Lozano, Rafael Rosell, Joan Maurel

Department of Gastroenterology, Hospital Clínic Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
2013-7-21; doi: 10.1016/j.ejca.2014.04.019

Abstract

Introduction

Chemotherapy is the principal treatment in metastatic colorectal cancer (mCRC) patients. RAC1b, a RAC1 spliced variant, is over-expressed in colorectal cancer (CRC), and impairs apoptosis by activation of nuclear-factor-KB. Since RAC1b has been associated with the BRAF(V600E) mutation, associated with poor prognosis in CRC, we evaluated the role of RAC1b expression as a predictor of chemotherapy efficacy in mCRC.

Methods

We analysed KRAS and BRAF mutation, microsatellite instability and RAC1b expression in 157 mCRC patients treated with FOLFOX/XELOX in first-line therapy.

Results

KRAS mutations were detected in 46 patients (34%), 10 patients were BRAF mutant (7%) and 79 were WT for both, KRAS and BRAF (59%). RAC1b overexpression was found in 30 patients (19%). In the multivariate analysis, BRAF mutational status was a poor prognostic factor for overall survival (OS); hazard ratio (HR), 2.78 (95% confidence interval (CI), 1.35-5.72; p=0.0057). RAC1b overexpression was a poor survival factor for OS (HR, 2.35; 95% CI, 1.2-4.59; p=0.01) and progression-free survival (PFS) (HR, 2.4; 95% CI, 1.2-4.78; p=0.01) in KRAS/BRAF WT mCRC patients.

Conclusions

RAC1b overexpression constitutes a marker of poor prognosis in KRAS/BRAF WT mCRC patients treated with first-line FOLFOX/XELOX therapy.