Division of Surgical Oncology, Ohio State University Medical Center, OH, USA.
HPB (Oxford). 2013 Apr;15(4):260-4. doi: 10.1111/j.1477-2574.2012.00523.x. Epub 2012 Jul 4.
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.
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 Kaplan-Meier method; factors, including miRNA expression, were compared by log-rank, chi-squared or Cox regression analyses.
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 [41.5 months vs. 12.3 months (P= 0.002) and 21.9 months vs. 15.1 months (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 (58.7 months vs. 15.1 months; P < 0.000; n= 8); clinicopathologic factors in these groups were otherwise similar.
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.
微小 RNA（miRNA）是一类在癌症中失调的小非编码基因，可能预测生存。miRNA 在胆管癌（CC）中的作用尚未有报道。
从 32 例切除的 CC 及其相邻的无病变胆管上皮中提取 RNA。使用 NanoString™ 定量了 43 种 miRNA。记录了临床病理特征和结局，并进行了比较。使用 Kaplan-Meier 法绘制总生存曲线；使用对数秩检验、卡方检验或 Cox 回归分析比较包括 miRNA 表达在内的因素。
排除围手术期死亡（n=3）后，将每种 miRNA 的绝对表达与总生存进行比较。与相邻正常胆管上皮相比，在切除的 CC 中，1 种上调（miR-151-3p；P=0.003）和 1 种下调（miR-126；P=0.023）的 miRNA 与单因素分析中的生存相关。比较临床因素和这些 miRNA。失调的 miR-151-3p 和 miR-126 分别是与总体生存改善相关的唯一因素[41.5 个月与 12.3 个月（P=0.002）和 21.9 个月与 15.1 个月（P=0.02）]。在 8 例患者中，两种 miRNA 均失调。在其余患者中，只有一种或两种均未失调。同时失调与最佳总生存相关（58.7 个月与 15.1 个月；P<0.000；n=8）；这些组中的临床病理因素否则相似。
在切除的 CC 中，miR-151-3p 和 miR-126 同时失调是与总生存改善最大相关的因素。对这些 miRNA 的靶标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。
