RAC1b overexpression correlates with poor prognosis in KRAS/BRAF WT metastatic colorectal cancer patients treated with first-line FOLFOX/XELOX chemotherapy
RAC1b overexpression correlates with poor prognosis in KRAS/BRAF WT metastatic colorectal cancer patients treated with first-line FOLFOX/XELOX chemotherapy
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DOI：
10.1016/j.ejca.2014.04.019
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发表时间：
2014-07-01
影响因子：
8.4
通讯作者：
Maurel, Joan
中科院分区：
文献类型：
--
作者：
Alonso-Espinaco, Virginia;Cuatrecasas, Miriam;Maurel, Joan
简介：化疗是转移性结直肠癌（mCRC）患者的主要治疗方法。 RAC1b 是 RAC1 剪接变体，在结直肠癌 (CRC) 中过度表达，并通过激活核因子 KB 来损害细胞凋亡。由于 RAC1b 与 BRAF(V600E) 突变相关，且与 CRC 不良预后相关，因此我们评估了 RAC1b 表达作为 mCRC 化疗疗效预测因子的作用。方法：我们分析了 157 例一线接受 FOLFOX/XELOX 治疗的 mCRC 患者的 KRAS 和 BRAF 突变、微卫星不稳定性和 RAC1b 表达。 在 46 名患者 (34%) 中检测到，10 名患者为 BRAF 突变体 (7%)，79 名患者 KRAS 和 BRAF 均为 WT (59%)。 30 名患者 (19%) 发现 RAC1b 过度表达。在多变量分析中，BRAF 突变状态是总生存期 (OS) 的不良预后因素；风险比 (HR)，2.78（95% 置信区间 (CI)，1.35-5.72；p = 0.0057）。 RAC1b 过表达是 KRAS/BRAF WT mCRC 患者 OS（HR，2.35；95% CI，1.2-4.59；p = 0.01）和无进展生存（PFS）（HR，2.4；95% CI，1.2-4.78；p = 0.01）的不良生存因素。结论：RAC1b 过表达是 KRAS/BRAF WT mCRC 患者预后不良的标志。 接受一线 FOLFOX/XELOX 治疗的 KRAS/BRAF WT mCRC 患者。 (C) 2014 Elsevier Ltd. 保留所有权利。
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. (C) 2014 Elsevier Ltd. All rights reserved.