High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer
High expression of microRNA-625-3p is associated with poor response to first-line oxaliplatin based treatment of metastatic colorectal cancer
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DOI：
10.1016/j.molonc.2013.02.016
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发表时间：
2013-06-01
影响因子：
6.6
通讯作者：
Andersen, Claus L.
中科院分区：
文献类型：
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作者：
Rasmussen, Mads H.;Jensen, Niels F.;Andersen, Claus L.
目前转移性结直肠癌(MCRC)的细胞毒治疗的主干包括氟嘧啶联合奥沙利铂(XELOX/FOLFOX)或伊立替康(XELIRI/FOLFIRI)。由于两种治疗组合的总体客观有效率约为50%，一个尚未解决的主要问题是，没有可用的对这些治疗有效的预测指标。为了解决这个问题，我们在接受XELOX/FOLFOX作为mCRC一线治疗的应答者和无应答者的激光捕获显微切割癌细胞中分析了742个microRNA，并发现miR-625-3p、miR-181b和miR-27b的高表达与临床反应差有关。在94名接受XELOX一线治疗的mCRC患者的验证队列中，miR-625-3p的高表达被证实与不良反应相关(OR=6.25，95%CI[1.8；21.0])。独立分析显示，miR-625-3p在正常和癌组织中没有表达异常，其表达与II期或III期疾病的复发无关，表明miR-625-3p单独是一种反应标志。最后，我们还发现这些miRNAs在奥沙利铂耐药的HCT116/oxPT(miR-625-3p、miR-181b和miR-27b)和LoVo/oxPT(miR-181b)结肠癌细胞系中的表达水平高于其同基因亲本细胞。综上所述，我们的结果提示miR-625-3p与mCRC一线奥沙利铂化疗的疗效有关。(C)2013年欧洲生化学会联合会。爱思唯尔出版，版权所有。
The backbone of current cytotoxic treatment of metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine together with either oxaliplatin (XELOX/FOLFOX) or irinotecan (XELIRI/FOLFIRI). With an overall objective response rate of approximately 50% for either treatment combination, a major unsolved problem is that no predictors of response to these treatments are available. To address this issue, we profiled 742 microRNAs in laser-capture microdissected cancer cells from responding and non-responding patients receiving XELOX/FOLFOX as first-line treatment for mCRC, and identified, among others, high expression of miR-625-3p, miR-181b and miR-27b to be associated with poor clinical response. In a validation cohort of 94 mCRC patients treated first-line with XELOX, high expression of miR-625-3p was confirmed to be associated with poor response (OR = 6.25, 95%CI [1.8; 21.0]). Independent analyses showed that miR-625-3p was not dysregulated between normal and cancer samples, nor was its expression associated with recurrence of stage II or III disease, indicating that miR-625-3p solely is a response marker. Finally, we also found that these miRNAs were up-regulated in oxaliplatin resistant HCT116/oxPt (miR-625-3p, miR-181b and miR-27b) and LoVo/oxPt (miR-181b) colon cancer cell lines as compared with their isogenic parental cells. Altogether, our results suggest an association between miR-625-3p and response to first-line oxaliplatin based chemotherapy of mCRC. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.