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

Authors: Alonso-Espinaco, Virginia  Cuatrecasas, Miriam  Alonso, Vicente  Escudero, Pilar  Marmol, Maribel  Horndler, Carlos  Ortego, Javier  Gallego, Rosa  Codony-Servat, Jordi  Garcia-Albeniz, Xabier  Jares, Pedro  Castells, Antoni  Lozano, Juan José  Rosell, Rafael  Maurel, Joan 
Citation: Alonso-Espinaco V, etal., Eur J Cancer. 2014 Jul;50(11):1973-81. doi: 10.1016/j.ejca.2014.04.019. Epub 2014 May 12.
Pubmed: (View Article at PubMed) PMID:24833563
DOI: Full-text: DOI:10.1016/j.ejca.2014.04.019


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.

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CRRD Object Information
CRRD ID: 13432050
Created: 2017-09-14
Species: All species
Last Modified: 2017-09-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.