MicroRNA Expression Patterns to Differentiate Pancreatic Adenocarcinoma From Normal Pancreas and Chronic Pancreatitis

Bloomston, Mark; Frankel, Wendy L.; Petrocca, Fabio; Volinia, Stefano; Alder, Hansjüerg; Hagan, John P.; Liu, Chang Gong; Bhatt, Darshna; Taccioli, Cristian; Croce, Carlo M.

doi:10.1001/jama.297.17.1901

Cited by 1,070 publications

(1,004 citation statements)

References 26 publications

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“…[15][16][17][18][19] In pancreatic adenocarcinomas, the expression of miR-15b, miR-21, miR-95, miR-103, miR-107, miR-148a, miR-155, miR-196a, miR-200, miR-210, miR-217, miR-221, miR-222 and miR-375 are different from tissue of normal pancreas and chronic pancreatitis. 17,[20][21][22][23][24][25][26][27] The results reported by Bloomston et al 20 and Szafranska et al 26 give promises of significant clinical impact of microRNA expression profiles to separate tissue from pancreatic adenocarcinomas from normal pancreas and chronic pancreatitis. The study by Szafranska et al 26 included a combination of two microRNAs (the difference between miR-196a and miR-217) to separate pancreatic adenocarcinomas and chronic pancreatitis (ASURAGEN-test).…”

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confidence: 96%

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MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

Schultz

Werner

Willenbrock³

et al. 2012

Modern Pathology

137

106

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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.

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confidence: 96%

“…20,21,23,24 MicroRNAs are stable in formalin-fixed paraffin-embedded samples. 28,29 Tumor cells in pancreatic ductal adenocarcinomas are often located in small groups surrounded by an abundant stromal tissue 30 and information related to microRNAs from the stromal tissue may be lost if micro-dissection is applied.…”

mentioning

confidence: 99%

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

Schultz

Werner

Willenbrock³

et al. 2012

Modern Pathology

137

106

View full text Add to dashboard Cite

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“…81 miRs had low expression and were categorized as not reliably detected. Interestingly, several miRs previously reported as associated with PDAC including, miR‐221‐3p, 210, ‐23a‐3p, ‐143‐3p, and ‐21‐5p were among those highly expressed in the CTC samples (Figure 4C) 17, 18, 19, 20. Additionally, based on pathway analysis, the top network functions enriched in the profiles were for cancer and organismal injury and abnormalities.…”

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confidence: 85%

“…Moreover, for the first time we report that PDAC CTC miRNA profiling revealed a trend toward high expression of miRs 17‐5p, 19b‐3p, 320b, and let7a‐5p. Also, miR‐96‐3p, 216b, 155‐5p, 212‐3p, and ‐31‐5p which demonstrated decreased expression have been previously reported to exhibit down regulation in pancreatic cancer 17, 18…”

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confidence: 95%

Ultra‐Specific Isolation of Circulating Tumor Cells Enables Rare‐Cell RNA Profiling

Jack

Grafton

Rodrigues³

et al. 2016

Advanced Science

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The clinical potential of circulating tumor cells (CTCs) in managing cancer metastasis is significant. However, low CTC isolation purities from patient blood have hindered sensitive molecular assays of these rare cells. Described herein is the ultra‐pure isolation of CTCs from patient blood samples and how this platform has enabled highly specific molecular (mRNA and miRNA) profiling of patient CTCs.

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“…Profiling of PTC by He et al (2005a) yielded a signature of five miRNAs (which included miR-221, miR-222 and miR-146) that can separate PTC from normal thyroid. Bloomston et al (2007) showed that a signature of 21 upregulated and 4 downregulated miRNAs correctly differentiated pancreatic cancer from benign pancreatic tissue in 90% of samples. In the profile, two commonly malignancyassociated miRNAs, miR-21 and miR-155, were uniquely overexpressed in pancreatic cancer compared to normal pancreas.…”

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confidence: 99%

MicroRNAs as potential cancer therapeutics

2008

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MicroRNA Expression Patterns to Differentiate Pancreatic Adenocarcinoma From Normal Pancreas and Chronic Pancreatitis

Cited by 1,070 publications

References 26 publications

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

Ultra‐Specific Isolation of Circulating Tumor Cells Enables Rare‐Cell RNA Profiling

MicroRNAs as potential cancer therapeutics

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