MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

Abstract

MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b* and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P ¼ 2.06 Â 10 À 54 ) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from nonneoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic and ampullary adenocarcinomas from chronic pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing prospective studies will evaluate if these microRNA profiles are useful on fine-needle biopsies for early diagnosis of pancreatic cancer. Modern Pathology (2012Pathology ( ) 25, 1609Pathology ( -1622 doi:10.1038/modpathol.2012; published online 10 August 2012Keywords: ampullary adenocarcinoma; chronic pancreatitis; microRNA; normal pancreas; pancreatic adenocarcinoma; pancreatic cancer Pancreatic cancer is the fourth most common cause of cancer death in United States and Europe. 1,2 Less than 20% of the patients can be operated with curative intent and the 5-year survival after surgery is below 20%. 3 Early diagnosis is difficult and the clinical and histological similarities between pancreatic cancer and chronic pancreatitis further complicate the differentiation between inflammation and cancer.

Involvement of MicroRNA-198 Overexpression in the Poor Prognosis of Esophageal Cancer

“…Consistent with our results, previous studies found that miR-198 expression is higher in cancer, including retinoblastoma (Zhao et al, 2009), squamous cell carcinoma of the tongue (Wong et al, 2008), pancreatic adenocarcinoma and ampullary adenocarcinoma (Schultz et al, 2012), and hepatocellular carcinoma (Varnholt et al, 2008). This condition is explained by miR-198 that regulates the Livin expression in cancer cells.…”

microRNAs with prognostic significance in pancreatic ductal adenocarcinoma: A meta-analysis

“…The results for tissue miR-196a [12] and miR-196b [41] were pooled, as these miRNAs differ by only one nt (which is not within the seed region) and both have been shown to separate PDAC from chronic pancreatitis and normal pancreas samples with good accuracy [50]. These two tissue studies used univariate analyses, and when combined produced an unadjusted estimate of risk of mortality of HR 1.43 (95% CI: 0.80-2.56, P = 0.232; Additional file 7: Fig.…”

Developments in Mirna Gene Signaling Pathways in Pancreatic Cancer

“…Twenty additional miRNAs were discovered to discriminate between PDAC, chronic pancreatic and normal pancreas [78]. Later, expression of miR-203 [78], miR-148a, miR-196b, miR-196a and miR-205 [79] were demonstrated to be altered in PDAC versus chronic pancreatitis. In addition, miRNA expression profiles have been recently used to distinguish PDAC from cholangiocarcinoma, two practically indistinguishable cancers using conventional histopathological and clinical characteristics [80].…”