转移性结直肠癌患者接受抗 EGFR 单克隆抗体治疗后的 microRNA 特征。
MicroRNA signature in metastatic colorectal cancer patients treated with anti-EGFR monoclonal antibodies.
机构信息
Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Italy.
Translational Oncogenomic Unit, National Cancer Institute Regina Elena, Rome, Italy.
出版信息
Clin Colorectal Cancer. 2014 Mar;13(1):37-45.e4. doi: 10.1016/j.clcc.2013.11.006. Epub 2013 Nov 14.
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.
背景
为了研究 microRNAs 是否可预测转移性结直肠癌（mCRC）患者对表皮生长因子受体（EGFR）单克隆抗体的敏感性。
方法
本研究纳入了接受西妥昔单抗或帕尼单抗治疗的 2 个独立队列（队列 1：74 例；验证队列：109 例）中的 183 例 mCRC 病例。使用 Agilent 的 miRNA 平台对 miRNA 芯片进行分析。
结果
该研究确定了 Let-7c/miR-99a/miR-125b 簇作为与抗 EGFR 治疗结果不同的特征签名。在第一队列中，高强度特征签名的患者无进展生存期（PFS）（6.1 与 2.3 个月；P =.02）和总生存期（OS）（29.8 与 7.0 个月，P =.08）显著长于低强度特征签名的患者。在验证队列中，高强度特征签名的患者 PFS 和 OS 明显长于低强度特征签名的患者（PFS 7.8 与 4.3 个月，P =.02；OS 12.8 与 7.5 个月，P =.02）。在 KRAS 野生型人群（n = 120）中，高强度特征签名患者的 PFS（7.8 与 4.6 个月，P =.016）和 OS（16.1 与 10.9 个月，P =.09）显著长于低特征签名患者，而 KRAS 突变型患者无差异。
结论
MiR-99a/Let-7c/miR-125b 特征签名可能有助于选择 KRAS 野生型 mCRC 患者作为抗 EGFR 治疗的良好候选者。
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