miR31-3p表达水平与抗表皮生长因子受体（EGFRs）治疗后KRAS野生型转移性结
研究方法
通过对125个福尔马林固定、石蜡包埋的原发肿瘤标本进行实时荧光聚合酶链反应来检测miR31-3p的表达。对照组中有63位患者，他们应用
研究结果
试验组中miR31-3p的表达与无进展生存期之间存在明显相关性(p=0.035; HR=1.2, CI95% CI[0.98–1.48])，而对照组中二者无相关性(p=0.36; HR=0.96, CI95% [0.75–1.23])。我们建立了进展高风险和低风险的预测模型。试验组中，miR31-3p高表达的患者的无进展生存期较低表达的患者短(p=0.033)。所有miR31-3p高表达的患者中，试验组患者的无进展生存期比对照组短(p=0.0177, 试验组无进展生存期的中位数为49.6周，而对照组无进展生存期的中位数为64.9周)。所有miR31-3p低表达的患者中，试验组和对照组患者的无进展生存期无明显差异。原发肿瘤和转移瘤的miR-31-3p表达的研究显示，对照组中二者具有相关性(p=0.00004)，而试验组中二者并无相关性(p=0.55)。
结论
我们首次发现miR31-3p表达是西妥昔单抗疗效的预测因素，应用西妥昔单抗的患者的无进展生存期与miR31-3p的表达存在相关性。利用miR31-3p的表达情况可以找出西妥昔单抗+化疗对无进展生存期存在不利影响的患者亚群。对照组患者转移瘤或原发肿瘤中miR31-3p的表达有相关性，而试验组中二者无相关性，提示西妥昔单抗影响miR31-3p的表达，这一点支持其参与EGFR通路。
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会议专题》》》2014年ASCO年会专题报道
阅读英文摘要
Mir-31-3p as a predictive biomarker of cetuximab effects in a post hoc analysis of new EPOC phase III trial.(Abstract No:3523)
Authors: Pierre Laurent-Puig, John A. Bridgewater,et al.
Session Type: Poster Highlights Session
Background: miR31-3p expression level has been associated with progression free survival (PFS) in KRAS wild type metastatic colorectal cancer (mCRC) patients treated with anti-epidermal growth factor receptors (EGFRs). In this study we evaluated its predictive value on PFS in the new EPOC trial by measuring its expression in primary tumors and liver metastases.
Methods: miR31-3p expression was determined by RT-QPCR in 125 formalin-fixed and paraffin-embedded (FFPE) primary tumor samples from patients. There were 63 patients (control arm) who received oxaliplatin or irinotecan-based chemotherapy and 62 received the above plus cetuximab. Correlations between miRNA expression and survival were performed using an adjusted Cox model. Liver metastasis were available for 58 of the 125 patients and comparison was done using a Pearson correlation on log2 transformed miR31-3p expression value.
Results: A significant association was found between PFS and miR31-3p expression in the cetuximab arm (p=0.035; HR=1.2, CI95% CI [0.98 – 1.48]), and not in the control arm (p=0.36; HR=0.96, CI95% [0.75 – 1.23]).A predictive model was developed dichotomizing patients with high or low risk of progression. In the cetuximab arm PFS was significantly shorter in patients with high expression than in patients with low expression (p=0.033). In all patients with high miR31-3p expression, PFS was significantly shorter in the cetuximab treated arm than in the control arm (p=0.0177, median PFS: 49.6 and 64.9 weeks respectively), in all patients with low miR31-3p expression, PFS was not different between cetuximab and control arm. Study of miR-31-3p expression in primary tumor and matching metastasis showed a correlation in the control arm (p=0.00004) but not in the cetuximab arm (p=0.55).
Conclusions: We demonstrated for the first time that miR31-3p expression is predictive of cetuximab effects and replicated association of its expression with PFS in patients receiving cetuximab. Furthermore miR31-3p allowed identification of a subgroup of patients in which cetuximab with chemotherapy had a detrimental effect on PFS. Eventually the correlation of miR31-3p expression in metastases and primary tumors in the control arm, but not in the cetuximab arm, suggests cetuximab has an effect on miR31-3p expression, supporting its involvement in the EGFR pathway.
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