MicroRNA Signature in Metastatic Colorectal Cancer Patients Treated With Anti-EGFR Monoclonal Antibodies
MicroRNA Signature in Metastatic Colorectal Cancer Patients Treated With Anti-EGFR Monoclonal Antibodies
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DOI：
10.1016/j.clcc.2013.11.006
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发表时间：
2014-03-01
影响因子：
3.4
通讯作者：
Blandino, Giovanni
中科院分区：
文献类型：
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作者：
Cappuzzo, Federico;Sacconi, Andrea;Blandino, Giovanni
本研究评估了两个不同队列的接受西妥昔单抗或帕尼单抗治疗的转移性结直肠癌患者的微小RNA表达和结局。在整个人群和KRAS野生型患者中，高强度水平的签名miR-99 a/Let-7 c/miR-125 b与显著延长的无进展生存期和总生存期相关。miR-99 a/Let-7 c/miR-125 b特征可以提高KRAS野生型患者抗EGFR治疗的选择性。背景：研究microRNA是否可以预测转移性结直肠癌（mCRC）患者对抗表皮生长因子受体（EGFR）单克隆抗体的敏感性。研究方法：本研究共纳入了来自2个独立队列（队列1：74例病例;验证队列：109例病例）的183例接受西妥昔单抗或帕尼单抗治疗的mCRC病例。使用Agilent的miRNA平台分析miRNA阵列。结果如下：该研究将Let-7 c/miR-99 a/miR-125 b簇确定为与抗EGFR治疗结果不同的结果相关的特征。在第一个队列中，与低强度特征的患者相比，高强度特征的患者的无进展生存期（PFS）（6.1 vs. 2.3 mo; P= 0.02）和总生存期（OS）（29.8 vs. 7.0 mo，P= 0.08）显著延长。在验证队列中，具有高强度特征的患者的PFS和OS显著长于具有低强度特征的个体（PFS 7.8 vs. 4.3个月，P= 0.02; OS 12.8 vs. 7.5个月，P= 0.02）。在KRAS野生型人群（n = 120）中，与低特征个体相比，高强度特征患者的PFS（7.8 vs. 4.6 mo，P= 0.016）和OS（16.1 vs. 10.9 mo，P= 0.09）显著延长，KRAS突变患者无差异。结论：MiR-99 a/Let-7 c/miR-125 b特征可以改善KRAS野生型mCRC患者作为抗EGFR治疗良好候选者的选择。(C)2014爱思唯尔公司All rights reserved.
This study evaluated micro-RNAs expression and outcome in two different cohorts of metastatic colorectal cancer patients treated with cetuximab or panitumumab. High intensity levels of the signature MiR-99a/Let-7c/miR-125b associated with significant longer progression-free survival and overall survival in the whole population and in KRAS wild-type patients. MiR-99a/Let-7c/miR-125b signature may improve the selection of KRAS wild-type patients for anti-EGFR therapy.Background: To investigate whether microRNAs are predictive of sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies in patients with metastatic colorectal cancer (mCRC). Methods: A total of 183 mCRC cases from 2 independent cohorts (cohort 1: 74 cases; validation cohort: 109 cases) treated with cetuximab or panitumumab were included in the study. MiRNA arrays were analyzed using Agilent's miRNA platform. Results: The study identified the cluster Let-7c/miR-99a/miR-125b as a signature associated with an outcome different from that of anti-EGFR therapies. In the first cohort, patients with high-intensity signatures had a significantly longer progression-free survival (PFS) (6.1 vs. 2.3 mo; P=.02) and longer overall survival (OS) (29.8 vs. 7.0 mo, P=.08) than patients with low-intensity signatures. In the validation cohort, patients with high signature had significantly longer PFS and OS than individuals with low-intensity signatures (PFS 7.8 vs. 4.3 mo, P=.02; OS 12.8 vs. 7.5 mo, P=.02). In the KRAS wild-type population (n = 120), high-intensity signature patients had a significantly longer PFS (7.8 vs. 4.6 mo, P=.016) and longer OS (16.1 vs. 10.9 mo, P=.09) than low-signature individuals, with no difference in KRAS mutated patients. Conclusion: The MiR-99a/Let-7c/miR-125b signature may improve the selection of patients with KRAS wild-type mCRC as good candidates for anti-EGFR therapy. (C) 2014 Elsevier Inc. All rights reserved.