Concomitant dysregulation of microRNAs miR-151-3p and miR-126 correlates with improved survival in resected cholangiocarcinoma

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.