MicroRNA-27b as a prognostic marker in pancreatic neuroendocrine tumor.

Abstract

251 Background: Pancreatic neuroendocrine tumors (PNETs) are heterogeneous group of tumors with a wide spectrum of behavioral characteristics. PNET generally behaves in an indolent fashion. However, when metastasis occurs, it is difficult to be treated. Little is known about prognostic biomarker in PNET. The aim of this study was to elucidate prognostic biomarker in PNET using nanostring microRNA (miRNA) array technology. Methods: We had already selected several candidate miRNAs (miR-27b, miR-122, miR-142-5p, miR-196a, miR-223, miR-590-5p, miR-630 and miR-944), which indicated 3 folds expression differences between primary tumor and metastatic tumor on the basis of nanostring-based microarray in two PNET patients. Further 39 PNET patients were enrolled for clinical validation (recurrence group includes patients who had metastasis subsequently; no-recurrence group includes the others) of 8 miRNAs. Surrounding pancreas and tumor miRNA were isolated separately from formalin-fixed paraffin-embedded tissues. Expression of candidate miRNAs was measured by quantitative real-time PCR using U6 as an internal control. Mann-Whitney U test and Spearman rank correlation analysis were used for statistical evaluation at p < 0.05 level. Results: miR-27b expression was elevated in recurrence group compared to no-recurrence group (p = 0.019). And also, miR-27b expression was statistically significant correlated positively with CA 19-9 level (p = 0.015). The Hierarchical cluster analysis of eight miRNAs showed miR-27b linked functionally to miR-142-5p and miR-196a. Furthermore, miR-196 expression was associated with Ki-67 index with a statistical significance (p = 0.035). Conclusions: The miR-27b would be a prognostic marker of recurrence in resected PNET and link to miR-142-5p and miR-196a, which correlated with Ki-67 index. Further experimental investigation would be required to demonstrate the role of these miRNAs in PNET.