MicroRNA-21 is Overexpressed in Pancreatic Cancer and a Potential Predictor of Survival
MicroRNAs are small (18–22 nucleotides) noncoding RNAs involved in posttranscriptional modification of many target genes. One of these, microRNA-21 (miR-21), has been shown to play a role in multiple hematologic and solid organ malignancies. We sought to determine the expression pattern of miR-21 in pancreatic cancers and its impact on clinicopathologic characteristics.
Eighty resected pancreatic cancer specimens were microdissected and tissue microarrays (TMA) created in duplicate. TMAs were also created for benign pancreas (N = 12) and chronic pancreatitis (N = 45). In situ hybridization (ISH) was undertaken utilizing locked nucleic acid probes for miR-21. RNA U6 and scrambled RNA served as positive and negative control, respectively. ISH was scored as 0 (absent), 1+ (faint/focal expression), or 2+ (strong expression). Kaplan–Meier survival curves were constructed and compared by log-rank analysis.
MiR-21 expression was demonstrated in 63 (79%) pancreatic cancers (1+ in 49, 2+ in 14) compared to one of 12 (8%, p < 0.0001) benign pancreas and 12/45 (27%, p < 0.0001) chronic pancreatitis. None of the benign tissues demonstrated strong miR-21 expression. Although miR-21 expression did not correlate with tumor size, differentiation, nodal status, or T stage, strong miR-21 expression was predictive of poorer outcome compared to absent or faint/focal miR-21 expression in patients with node-negative disease (median 27.7 months vs. 15.2, p = 0.037). Nodal status was also predictive of survival (p = 0.029).
MicroRNA-21 is significantly overexpressed in pancreatic cancers as detected by in situ hybridization. Its strong expression predicts limited survival in patients with node-negative disease and may be an important biologic marker for outcome.
KeywordsMicroRNA MiRNA MiR-21 Pancreatic cancer
- 2.Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 1997;225(5):621–33. doi: 10.1097/00000658-199705000-00018.PubMedCrossRefGoogle Scholar
- 4.Dillhoff M, Wojcik S, Bloomston M. MiRNAs in solid tumors. J Surg Res 2008;in press.Google Scholar
- 12.Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 2006;24(29):4677–4684. doi: 10.1200/JCO.2005.05.5194.PubMedCrossRefGoogle Scholar
- 15.Nuovo GJ. PCR In Situ Hybridization: Protocols and Applications. 3rd ed. Lippincott, New York: Williams and Wilkins, Raven, 1996.Google Scholar