Concomitant dysregulation of microRNAs miR-151-3p and miR-126 correlates with improved survival in resected cholangiocarcinoma
Concomitant dysregulation of microRNAs miR-151-3p and miR-126 correlates with improved survival in resected cholangiocarcinoma
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DOI：
10.1111/j.1477-2574.2012.00523.x
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发表时间：
2013-04-01
期刊：
影响因子：
2.9
通讯作者：
Bloomston, Mark
中科院分区：
文献类型：
--
作者：
McNally, Megan E.;Collins, Amy;Bloomston, Mark
背景：MicroRNA (miRNA) 是一种小型非编码基因，在癌症中失调并可预测生存。 miRNA 在胆管癌 (CC) 预后中的作用尚未有报道。方法：从 32 个切除的 CC 以及邻近的未受累胆管上皮中提取 RNA。使用 NanoString 对总共 43 个 miRNA 进行了定量。捕获并比较临床病理特征和结果。使用 KaplanMeier 方法创建总体生存曲线；通过对数秩、卡方或 Cox 回归分析来比较包括 miRNA 表达在内的因素。结果：将每种 miRNA 的绝对表达与排除围手术期死亡后的总生存率进行比较 (n=3)。单变量分析显示，相对于邻近正常胆管上皮，切除的 CC 中 1 个上调 (miR-151-3p；P=0.003) 和 1 个下调 (miR-126；P=0.023) miRNA 与生存相关。比较了临床因素和这些 miRNA。失调的 miR-151-3p 和 miR-126 分别是与总生存期改善相关的唯一因素 [分别为 41.5 个月 vs. 12.3 个月 (P= 0.002) 和 21.9 个月 vs. 15.1 个月 (P= 0.02)]。在 8 名患者中，两种 miRNA 均失调。其余的人中，只有一个或没有一个表现出调节失调。伴随的失调与最佳总生存期相关（58.7 个月 vs. 15.1 个月；P < 0.000；n= 8）；这些组的临床病理因素在其他方面相似。结论：在切除的 CC 中，伴随的 miR-151-3p 和 miR-126 失调是与总体生存率最大改善相关的因素。对这些 miRNA 靶点的进一步分析可能会产生潜在的治疗靶点或预后生物标志物。
Background: MicroRNAs (miRNAs) are small non-coding genes which become dysregulated in cancer and may predict survival. The role of miRNAs in outcomes in cholangiocarcinoma (CC) has not been reported. Methods: RNA was extracted from 32 resected CCs along with adjacent uninvolved bile duct epithelium. A total of 43 miRNAs were quantified using NanoString. Clinicopathologic characteristics and outcomes were captured and compared. Overall survival curves were created using the KaplanMeier method; factors, including miRNA expression, were compared by log-rank, chi-squared or Cox regression analyses. Results: Absolute expression of each miRNA was compared with overall survival after excluding perioperative deaths (n= 3). One upregulated (miR-151-3p; P= 0.003) and one downregulated (miR-126; P= 0.023) miRNA in resected CC relative to adjacent normal bile duct epithelium correlated with survival on univariate analysis. Clinical factors and these miRNAs were compared. Dysregulated miR-151-3p and miR-126, respectively, were the only factors that correlated with improved overall survival [41.5months vs. 12.3months (P= 0.002) and 21.9months vs. 15.1months (P= 0.02), respectively]. In eight patients, both miRNAs were dysregulated. In the remainder, only one or neither showed dysregulation. Concomitant dysregulation correlated with the best overall survival (58.7months vs. 15.1months; P < 0.000; n= 8); clinicopathologic factors in these groups were otherwise similar. Conclusions: In resected CC, the concomitant dysregulation of both miR-151-3p and miR-126 was the factor related to the greatest improvement in overall survival. Further analysis of the targets of these miRNAs may yield potential therapeutic targets or prognostic biomarkers.