MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab.
MicroRNA expression profiling identifies miR-31-5p/3p as associated with time to progression in wild-type RAS metastatic colorectal cancer treated with cetuximab.
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DOI：
10.18632/oncotarget.5735
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发表时间：
2015-11-17
期刊：
影响因子：
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通讯作者：
Slaby O
中科院分区：
文献类型：
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作者：
Mlcochova J;Faltejskova-Vychytilova P;Ferracin M;Zagatti B;Radova L;Svoboda M;Nemecek R;John S;Kiss I;Vyzula R;Negrini M;Slaby O
本研究的目的是研究microRNAs （miRNAs）是否可以作为RAS野生型（wt-RAS）转移性结直肠癌（mCRC）患者抗egfr治疗（西妥昔单抗，帕尼单抗）的预测性生物标志物。纳入93例mCRC患者的历史队列（2006-2009），并进一步分为探索性和验证性队列。对41例接受西妥昔单抗治疗的wt-KRAS mCRC患者进行了MiRNAs表达谱分析，以确定与进展时间（TTP）相关的MiRNAs。验证在两个独立的队列中进行：28例使用西妥昔单抗治疗的wt-RAS mCRC患者和24例使用帕尼单抗治疗的wt-RAS mCRC患者。我们发现9个mirna在西妥昔单抗治疗反应者和无反应者之间表达有显著差异（P≤0.01）。在两个独立的患者队列中进一步评估了这9种miRNAs， miR-31-3p （P < 0.001）和miR-31-5p （P < 0.001）在接受西妥昔单抗而非帕尼单抗治疗的wt-RAS mCRC患者中被成功证实与TTP密切相关。当对西妥昔单抗患者的完整队列（N = 69）进行评估时，miR-31-3p （HR, 5.10; 95% CI, 2.52-10.32; P < 0.001）和miR-31-5p （HR, 4.80; 95% CI, 2.50-9.24; P < 0.001）与TTP在可比显著水平上相关。miR-31-5p/3p在RAS突变和野生型肿瘤样本中的表达水平无差异。MiR-31-5p/3p是wt-RAS mCRC患者西妥昔单抗反应的有希望的预测性生物标志物。
The aim of our study was to investigate whether microRNAs (miRNAs) could serve as predictive biomarkers to anti-EGFR therapy (cetuximab, panitumumab) in patients with RAS wild-type (wt-RAS) metastatic colorectal cancer (mCRC). Historical cohort of 93 patients with mCRC (2006–2009) was included and further divided into exploratory and validation cohorts. MiRNAs expression profiling was performed on the exploratory cohort of 41 wt-KRAS mCRC patients treated with cetuximab to identify miRNAs associated with time to progression (TTP). The validation was performed on two independent cohorts: 28 patients of wt-RAS mCRC treated with cetuximab and 24 patients of wt-RAS mCRC treated with panitumumab. We identified 9 miRNAs with significantly different expression between responders and non-responders to cetuximab therapy (P ≤ 0.01). These 9 miRNAs were further evaluated in two independent cohorts of patients and miR-31-3p (P < 0.001) and miR-31-5p (P < 0.001) were successfully confirmed as strongly associated with TTP in wt-RAS mCRC patients treated with cetuximab but not panitumumab. When evaluated on the complete cohort of cetuximab patients (N = 69), miR-31-3p (HR, 5.10; 95% CI, 2.52–10.32; P < 0.001) and miR-31-5p (HR, 4.80; 95% CI, 2.50–9.24; P < 0.001) were correlated with TTP on the comparable level of significance. There was no difference in miR-31-5p/3p expression levels in RAS mutated and wild-type tumor samples. MiR-31-5p/3p are promising predictive biomarkers of cetuximab response in wt-RAS mCRC patients.