Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Feb 15;18(4):981-92.
doi: 10.1158/1078-0432.CCR-11-2347. Epub 2011 Nov 23.

MicroRNA alterations of pancreatic intraepithelial neoplasias

Jun Yu  1 , Ang Li, Seung-Mo Hong, Ralph H Hruban, Michael Goggins
Affiliations

MicroRNA alterations of pancreatic intraepithelial neoplasias

Jun Yu et al. Clin Cancer Res. .

Abstract

Purpose: MicroRNA (miRNA) alterations are likely to contribute to the development of pancreatic cancer and may serve as markers for the early detection of pancreatic neoplasia.

Experimental design: To identify the miRNA alterations that arise during the development of pancreatic cancer, we determined the levels of 735 miRNAs in 34 pancreatic intraepithelial neoplasias (PanIN) and 15 normal pancreatic duct samples isolated by laser capture microdissection using TaqMan miRNA microarrays. Differential expression of selected miRNAs was confirmed by FISH analysis and by quantitative real-time reverse transcription PCR (qRT-PCR) analysis of selected candidate miRNAs in an independent set of PanIN and normal duct samples.

Results: We identified 107 aberrantly expressed miRNAs in different PanIN grades compared with normal pancreatic duct samples and 35 aberrantly expressed miRNAs in PanIN-3 lesions compared with normal pancreatic duct samples. These differentially expressed miRNAs included those that have been previously identified as differentially expressed in pancreatic ductal adenocarcinomas (PDAC; including miR-21, miR-200a/b/c, miR-216a/b, miR-217, miR-146a, miR-155, miR-182, miR-196b, miR-203, miR-222, miR-338-3p, miR-486-3p, etc.) as well as miRNAs not previously described as differentially expressed in these lesions (miR-125b, miR-296-5p, miR-183*, miR-603, miR-625/*, miR-708, etc.). miR-196b was the most selectively differentially expressed miRNA in PanIN-3 lesions.

Conclusions: Many miRNAs undergo aberrant expression in PanIN lesions and are likely to be important in the development of PDAC. The miRNAs, such as miR-196b, whose expression is limited to PanIN-3 lesions or pancreatic cancers could be useful as diagnostic markers.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: The authors disclose no conflicts

Figures

Figure 1
Figure 1. Validation of aberrantly expressed candidate miRNAs in PanIN lesions
The levels of candidate miR-146a, miR-182, miR-200a/b, miR-21, miR-29b, miR-486-3p, miR-708, and miR-874 expressions were measured in 9 normal pancreatic ducts (blue) and in 11 PanIN lesions (red). Each sample was run in triplicate. Horizontal bars represent medians.
Figure 2
Figure 2. Validation of aberrantly expressed candidate miRNAs in PanIN-3 lesions
The levels of miR-182, miR-196b, and miR-296-5p were measured in 24 normal pancreatic ducts (blue) and 13 PanIN-3 lesions (red). Each sample was run in triplicate. Horizontal bars represent medians.
Figure 3
Figure 3. Locked Nucleic Acid Fluorescent In Situ Hybridization (LNA-FISH) for miR-196b expression in Tissue microarrays
A, yellow arrows indicate LNA-miR-196b-FISH probe signals (green spots) for normal pancreatic ducts, PanIN-1 lesions, PanIN-2 lesions, PanIN-3 lesions, and PDAC lesions (from upper to lower, respectively), which are circled with white dashed lines. DAPI (blue) indicates nucleic acid staining. B, quantitative analysis of LNA-miR-196b-FISH probe with spots/cell in TMAs. The lower and upper borders of the boxes mark the 95% confidence interval of the mean. The center horizontal line is drawn at the sample mean. The vertical lines drawn from the boxes extend to the minimum and the maximum. AE, autofluorescence. Original magnification, 40×.
Figure 4
Figure 4. Progression of miRNA alterations during pancreatic carcinogenesis
Normal duct cells (far left), PanIN lesions (center), and invasive PDAC (far right). “+” and “−”: indicates presence or absence of miRNA expression in normal ducts, respectively. “↑” and “↓”, indicates changes in level of expression (2–10 fold and 0.1–0.5 fold, respectively). “↑↑” and “↓↓”, indicates changes in level of expression (>10-fold and <0.1-fold, respectively). * indicates P value < 0.05.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300. - PubMed
    1. Vincent A, Herman JM, Schulick R, Hruban R, Goggins M. Pancreatic Cancer. Lancet. 2011 in press. - PMC - PubMed
    1. Hruban RH, Takaori K, Klimstra DS, Adsay NVA-SJ, Biankin AV, Biankin SA, Compton C, Fukushima N, Furukawa T, Goggins M, Kato Y, Kloppel G, Longnecker DS, Luttges J, Maitra A, Offerhaus GJ, Shimizu M, Yonezawa S. An Illustrated Consensus on the Classification of Pancreatic Intraepithelial Neoplasia and Intraductal Papillary Mucinous Neoplasms. Am J Surg Pathol. 2004;28:977–987. - PubMed
    1. Canto MI, Goggins M, Hruban RH, Petersen GM, Giardiello FM, Yeo C, et al. Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol. 2006;4:766–781. quiz 665. - PubMed
    1. Canto MI, Goggins M, Yeo CJ, Griffin C, Axilbund JE, Brune K, et al. Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004;2:606–621. - PubMed

Publication types

MeSH terms