MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma

Jamieson, N. B. , Morran, D. C., Morton, J. P., Ali, A., Dickson, E. J., Carter, C. R., Sansom, O. J. , Evans, T. R. J. , McKay, C. J. and Oien, K. A. (2012) MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma. Clinical Cancer Research, 18(2), pp. 534-545. (doi:10.1158/1078-0432.CCR-11-0679)

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Publisher's URL: http://dx.doi.org/10.1158/1078-0432.CCR-11-0679

Abstract

Purpose: MicroRNAs (miRNA) have potential as diagnostic and prognostic biomarkers and as therapeutic targets in cancer. We sought to establish the relationship between miRNA expression and clinicopathologic parameters, including prognosis, in pancreatic ductal adenocarcinoma (PDAC).<p></p> Experimental Design: Global miRNA microarray expression profiling of prospectively collected fresh-frozen PDAC tissue was done on an initial test cohort of 48 patients, who had undergone pancreaticoduodenectomy between 2003 and 2008 at a single institution. We evaluated association with tumor stage, lymph node status, and site of recurrence, in addition to overall survival, using Cox regression multivariate analysis. Validation of selected potentially prognostic miRNAs was done in a separate cohort of 24 patients.<p></p> Results: miRNA profiling identified expression signatures associated with PDAC, lymph node involvement, high tumor grade, and 20 miRNAs were associated with overall survival. In the initial cohort of 48 PDAC patients, high expression of miR-21 (HR = 3.22, 95% CI: 1.21-8.58) and reduced expression of miR-34a (HR = 0.15, 95% CI: 0.06-0.37) and miR-30d (HR = 0.30, 95% CI: 0.12-0.79) were associated with poor overall survival following resection independent of clinical covariates. In a further validation set of 24 patients, miR-21 and miR-34a expression again significantly correlated with overall survival (P = 0.031 and P = 0.001).<p></p> Conclusion: Expression patterns of miRNAs are significantly altered in PDAC. Aberrant expression of a number of miRNAs was independently associated with reduced survival, including overexpression of miR-21 and underexpression of miR-34a.<p></p> Summary: miRNA expression profiles for resected PDAC were examined to identify potentially prognostic miRNAs. miRNA microarray analysis identified statistically unique profiles, which could discriminate PDAC from paired nonmalignant pancreatic tissues as well as molecular signatures that differ according to pathologic features. miRNA expression profiles correlated with overall survival of PDAC following resection, indicating that miRNAs provide prognostic utility.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Carter, Mr Christopher and Jamieson, Dr Nigel and Evans, Professor Thomas and Morran, Dr Douglas and Morton, Dr Jennifer and Oien, Dr Karin and Ali, Dr Asif and Sansom, Professor Owen
Authors: Jamieson, N. B., Morran, D. C., Morton, J. P., Ali, A., Dickson, E. J., Carter, C. R., Sansom, O. J., Evans, T. R. J., McKay, C. J., and Oien, K. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Clinical Cancer Research
Publisher:American Association for Cancer Research
ISSN:1078-0432
ISSN (Online):1557-3265
Published Online:23 November 2011
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
540161Investigating personalised therapy in mouse models of pancreatic cancer.Owen SansomMedical Research Council (MRC)G1000334Beatson Institute for Cancer Research
442831Gene expression and genetic profiling of pancreatic cancer for improved diagnosis, prediction of outcome and patient careKarin OienScottish Executive Health Department (SEHHD-CSO)CAF/06/24RI CANCER SCIENCES