MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma.

Abstract

INTRODUCTION:

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Diagnosis and management of PDAC are hampered by the absence of sensitive and specific disease biomarkers. MicroRNAs (miRNA) are noncoding regulatory RNAs involved in initiation and progression of human cancers. In this study, we sought to determine whether miR-10b could serve as a biomarker for PDAC.

EXPERIMENTAL DESIGN:

miRNA expression was characterized by fluorescence-based in situ hybridization using locked nucleic acid-modified DNA probes against miR-10b, miR-21, miR-155, miR-196a, and miR-210, followed by codetection of proteins by immunohistochemistry on the same tissue sections. miRNA expression in surgically resected PDAC tissues and in endoscopic ultrasonography (EUS)-guided fine-needle aspirate (EUS-FNA) samples was analyzed in cytokeratin 19 (CK19)-positive epithelial cells using optical intensity analysis.

RESULTS:

In 10 resected PDAC samples, miR-10b was the most frequently and consistently overexpressed miRNA among characterized miRNAs, exhibiting a four-fold increase in the cancer cells (P = 0.012). Given this preferential overexpression of miR-10b, we sought to determine whether miR-10b expression was clinically relevant. Accordingly, miR-10b expression was examined in 106 EUS-FNA samples obtained from pancreatic lesions. miR-10b expression was increased in cancer cells compared with CK19-positive epithelial cells in benign lesions (P = 0.0001). In patients with PDACs, lower levels of miR-10b were associated with improved response to multimodality neoadjuvant therapy, likelihood of surgical resection, delayed time to metastasis, and increased survival.

CONCLUSION:

miR-10b is a novel diagnostic biomarker for PDACs when assessing pancreatic lesions. Expression of miR-10b is predictive of response to neoadjuvant therapy and outcome in this disease.

• Authors: Meir Preis, Timothy B Gardner, Stuart R Gordon, J Marc Pipas, Todd A Mackenzie, Erin E Klein, Daniel S Longnecker, Edward J Gutmann, Lorenzo F Sempere, Murray Korc
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 17 Pg. 5812-21 (Sep 01 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21652542 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2011 AACR.

Chemical References

• Biomarkers, Tumor
• MIRN10 microRNA, human
• MIRN155 microRNA, human
• MIRN196 microRNA, human
• MIRN21 microRNA, human
• MIRN210 microRNA, human
• MicroRNAs

Topics

• Aged
• Aged, 80 and over
• Biomarkers, Tumor
• Carcinoma, Pancreatic Ductal (drug therapy, genetics, pathology)
• Female
• Gene Expression Profiling
• Humans
• In Situ Hybridization
• Male
• MicroRNAs (biosynthesis, genetics)
• Middle Aged
• Neoadjuvant Therapy
• Pancreatic Neoplasms (drug therapy, genetics, pathology)
• Treatment Outcome