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Published in: Diagnostic Pathology 1/2011

Open Access 01-12-2011 | Research

Changes of microRNAs-192, 196a and 203 correlate with Barrett's esophagus diagnosis and its progression compared to normal healthy individuals

Authors: Pavla Luzna, Jan Gregar, Ivo Uberall, Lenka Radova, Vlastimil Prochazka, Jiri Ehrmann Jr

Published in: Diagnostic Pathology | Issue 1/2011

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Abstract

Background

Barrett's esophagus (BE) is a disease with a rising prevalence in western countries probably due to the unhealthy lifestyle. In significant number of cases it develops to esophageal adenocarcinoma. Two decades ago, important gene regulators (microRNAs) were discovered and their attendance in the process of malignant transformation was demonstrated (e.g. miR-192, 196a, 203). Our aim was to select the patients with the increased risk of malignant transformation before the cancer develops.

Methods

71 patients with BE disease were selected, slides from FFPE blocks were prepared, the lesions were microdissected and a qPCR relative expression analysis for selected microRNAs (generally known to be connected with malignant transformation process) was carried out.

Results

We demonstrated unequivocal statistically significant upregulation of two microRNAs (miR-192, 196a) and downregulation of miR-203 and positive miR-196a correlation with progression from intestinal metaplasia to adenocarcinoma compared to normal individuals.

Conclusions

We hypothetize that there do exist changes of selected microRNAs which can undoubtedly distinguish the patients with BE from normal healthy individuals.
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Literature
1.
go back to reference Barrett N: Chronic peptic ulcer of the oesophagus and „oesophagitis“. Br J Surg. 1950, 30: 175-182.CrossRef Barrett N: Chronic peptic ulcer of the oesophagus and „oesophagitis“. Br J Surg. 1950, 30: 175-182.CrossRef
2.
go back to reference Sternberg SS: Histology for Pathology. 1997, Philadelphia: Lippincott Williams & Wilkins Sternberg SS: Histology for Pathology. 1997, Philadelphia: Lippincott Williams & Wilkins
3.
go back to reference Halvorsen JF, Semb BK: The "Barrett syndrome" (the columnar-lined lower oesophagus): an acquired condition secondary to reflux oesophagitis. A case report with discussion of pathogenesis. Acta Chir Scand. 1975, 141: 683-687.PubMed Halvorsen JF, Semb BK: The "Barrett syndrome" (the columnar-lined lower oesophagus): an acquired condition secondary to reflux oesophagitis. A case report with discussion of pathogenesis. Acta Chir Scand. 1975, 141: 683-687.PubMed
4.
go back to reference Gaddam S, Sharma P: Advances in endoscopic diagnosis and treatment of Barrett's esophagus. J Dig Dis. 2010, 11: 323-333. 10.1111/j.1751-2980.2010.00458.x.CrossRefPubMed Gaddam S, Sharma P: Advances in endoscopic diagnosis and treatment of Barrett's esophagus. J Dig Dis. 2010, 11: 323-333. 10.1111/j.1751-2980.2010.00458.x.CrossRefPubMed
5.
go back to reference Reid BJ, Li X, Galipeau PC, Vaughan TL: Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010, 10: 87-101. 10.1038/nrc2773.PubMedCentralCrossRefPubMed Reid BJ, Li X, Galipeau PC, Vaughan TL: Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010, 10: 87-101. 10.1038/nrc2773.PubMedCentralCrossRefPubMed
6.
go back to reference Spechler SJ, Fitzgerald RC, Prasad GA, Wang KK: History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus. Gastroenterology. 2010, 138: 854-869. 10.1053/j.gastro.2010.01.002.PubMedCentralCrossRefPubMed Spechler SJ, Fitzgerald RC, Prasad GA, Wang KK: History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus. Gastroenterology. 2010, 138: 854-869. 10.1053/j.gastro.2010.01.002.PubMedCentralCrossRefPubMed
7.
go back to reference Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK: The histologic spectrum of Barrett's esophagus. N Engl J Med. 1976, 295: 476-480. 10.1056/NEJM197608262950904.CrossRefPubMed Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK: The histologic spectrum of Barrett's esophagus. N Engl J Med. 1976, 295: 476-480. 10.1056/NEJM197608262950904.CrossRefPubMed
8.
go back to reference Adler RH: The lower esophagus lined by columnar epithelium. Its association with hiatal hernia, ulcer, stricture, and tumor. J Thorac Cardiovasc Surg. 1963, 45: 13-34.PubMed Adler RH: The lower esophagus lined by columnar epithelium. Its association with hiatal hernia, ulcer, stricture, and tumor. J Thorac Cardiovasc Surg. 1963, 45: 13-34.PubMed
9.
go back to reference Holmes RS, Vaughan TL: Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol. 2007, 17: 2-9. 10.1016/j.semradonc.2006.09.003.CrossRefPubMed Holmes RS, Vaughan TL: Epidemiology and pathogenesis of esophageal cancer. Semin Radiat Oncol. 2007, 17: 2-9. 10.1016/j.semradonc.2006.09.003.CrossRefPubMed
11.
go back to reference Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ: miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006, D140-144. 34 Database Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ: miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 2006, D140-144. 34 Database
12.
go back to reference Griffiths-Jones S: The microRNA Registry. Nucleic Acids Res. 2004, D109-111. 32 Database Griffiths-Jones S: The microRNA Registry. Nucleic Acids Res. 2004, D109-111. 32 Database
13.
go back to reference Bagnyukova TV, Pogribny IP, Chekhun VF: MicroRNAs in normal and cancer cells: a new class of gene expression regulators. Exp Oncol. 2006, 28: 263-269.PubMed Bagnyukova TV, Pogribny IP, Chekhun VF: MicroRNAs in normal and cancer cells: a new class of gene expression regulators. Exp Oncol. 2006, 28: 263-269.PubMed
15.
go back to reference Mirnezami AH, Pickard K, Zhang L, Primrose JN, Packham G: MicroRNAs: key players in carcinogenesis and novel therapeutic targets. Eur J Surg Oncol. 2009, 35: 339-347. 10.1016/j.ejso.2008.06.006.CrossRefPubMed Mirnezami AH, Pickard K, Zhang L, Primrose JN, Packham G: MicroRNAs: key players in carcinogenesis and novel therapeutic targets. Eur J Surg Oncol. 2009, 35: 339-347. 10.1016/j.ejso.2008.06.006.CrossRefPubMed
16.
go back to reference Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 2004, 101: 2999-3004. 10.1073/pnas.0307323101.PubMedCentralCrossRefPubMed Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 2004, 101: 2999-3004. 10.1073/pnas.0307323101.PubMedCentralCrossRefPubMed
17.
go back to reference Blenkiron C, Miska EA: miRNAs in cancer: approaches, aetiology, diagnostics and therapy. Hum Mol Genet. 2007, 16 (Spec No 1): R106-113.CrossRefPubMed Blenkiron C, Miska EA: miRNAs in cancer: approaches, aetiology, diagnostics and therapy. Hum Mol Genet. 2007, 16 (Spec No 1): R106-113.CrossRefPubMed
18.
go back to reference Kato M, Slack FJ: microRNAs: small molecules with big roles - C. elegans to human cancer. Biol Cell. 2008, 100: 71-81. 10.1042/BC20070078.CrossRefPubMed Kato M, Slack FJ: microRNAs: small molecules with big roles - C. elegans to human cancer. Biol Cell. 2008, 100: 71-81. 10.1042/BC20070078.CrossRefPubMed
19.
go back to reference Feber A, Xi L, Luketich JD, Pennathur A, Landreneau RJ, Wu M, Swanson SJ, Godfrey TE, Litle VR: MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg. 2008, 135: 255-260. 10.1016/j.jtcvs.2007.08.055.PubMedCentralCrossRefPubMed Feber A, Xi L, Luketich JD, Pennathur A, Landreneau RJ, Wu M, Swanson SJ, Godfrey TE, Litle VR: MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg. 2008, 135: 255-260. 10.1016/j.jtcvs.2007.08.055.PubMedCentralCrossRefPubMed
20.
go back to reference Maru DM, Singh RR, Hannah C, Albarracin CT, Li YX, Abraham R, Romans AM, Yao H, Luthra MG, Anandasabapathy S, Swisher SG, Hofstetter WL, Rashid A, Luthra R: MicroRNA-196a is a potential marker of progression during Barrett's metaplasia-dysplasia-invasive adenocarcinoma sequence in esophagus. Am J Pathol. 2009, 174: 1940-1948. 10.2353/ajpath.2009.080718.PubMedCentralCrossRefPubMed Maru DM, Singh RR, Hannah C, Albarracin CT, Li YX, Abraham R, Romans AM, Yao H, Luthra MG, Anandasabapathy S, Swisher SG, Hofstetter WL, Rashid A, Luthra R: MicroRNA-196a is a potential marker of progression during Barrett's metaplasia-dysplasia-invasive adenocarcinoma sequence in esophagus. Am J Pathol. 2009, 174: 1940-1948. 10.2353/ajpath.2009.080718.PubMedCentralCrossRefPubMed
21.
go back to reference Mathé EA, Nguyen GH, Bowman ED, Zhao Y, Budhu A, Schetter AJ, Braun R, Reimers M, Kumamoto K, Hughes D, Altorki NK, Casson AG, Liu CG, Wang XW, Yanaihara N, Hagiwara N, Dannenberg AJ, Miyashita M, Croce CM, Harris CC: MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res. 2009, 15: 6192-6200. 10.1158/1078-0432.CCR-09-1467.PubMedCentralCrossRefPubMed Mathé EA, Nguyen GH, Bowman ED, Zhao Y, Budhu A, Schetter AJ, Braun R, Reimers M, Kumamoto K, Hughes D, Altorki NK, Casson AG, Liu CG, Wang XW, Yanaihara N, Hagiwara N, Dannenberg AJ, Miyashita M, Croce CM, Harris CC: MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res. 2009, 15: 6192-6200. 10.1158/1078-0432.CCR-09-1467.PubMedCentralCrossRefPubMed
22.
go back to reference Yang H, Gu J, Wang KK, Zhang W, Xing J, Chen Z, Ajani JA, Wu X: MicroRNA expression signatures in Barrett's esophagus and esophageal adenocarcinoma. Clin Cancer Res. 2009, 15: 5744-5752. 10.1158/1078-0432.CCR-09-0385.PubMedCentralCrossRefPubMed Yang H, Gu J, Wang KK, Zhang W, Xing J, Chen Z, Ajani JA, Wu X: MicroRNA expression signatures in Barrett's esophagus and esophageal adenocarcinoma. Clin Cancer Res. 2009, 15: 5744-5752. 10.1158/1078-0432.CCR-09-0385.PubMedCentralCrossRefPubMed
23.
go back to reference Specht K, Richter T, Müller U, Walch A, Werner M, Höfler H: Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue. Am J Pathol. 2001, 158: 419-429. 10.1016/S0002-9440(10)63985-5.PubMedCentralCrossRefPubMed Specht K, Richter T, Müller U, Walch A, Werner M, Höfler H: Quantitative gene expression analysis in microdissected archival formalin-fixed and paraffin-embedded tumor tissue. Am J Pathol. 2001, 158: 419-429. 10.1016/S0002-9440(10)63985-5.PubMedCentralCrossRefPubMed
24.
go back to reference Abrahamsen HN, Steiniche T, Nexo E, Hamilton-Dutoit SJ, Sorensen BS: Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients. J Mol Diagn. 2003, 5: 34-41. 10.1016/S1525-1578(10)60449-7.PubMedCentralCrossRefPubMed Abrahamsen HN, Steiniche T, Nexo E, Hamilton-Dutoit SJ, Sorensen BS: Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients. J Mol Diagn. 2003, 5: 34-41. 10.1016/S1525-1578(10)60449-7.PubMedCentralCrossRefPubMed
25.
go back to reference Doleshal M, Magotra AA, Choudhury B, Cannon BD, Labourier E, Szafranska AE: Evaluation and validation of total RNA extraction methods for microRNA expression analyses in formalin-fixed, paraffin-embedded tissues. J Mol Diagn. 2008, 10: 203-211. 10.2353/jmoldx.2008.070153.PubMedCentralCrossRefPubMed Doleshal M, Magotra AA, Choudhury B, Cannon BD, Labourier E, Szafranska AE: Evaluation and validation of total RNA extraction methods for microRNA expression analyses in formalin-fixed, paraffin-embedded tissues. J Mol Diagn. 2008, 10: 203-211. 10.2353/jmoldx.2008.070153.PubMedCentralCrossRefPubMed
26.
go back to reference Siebolts U, Varnholt H, Drebber U, Dienes HP, Wickenhauser C, Odenthal M: Tissues from routine pathology archives are suitable for microRNA analyses by quantitative PCR. J Clin Pathol. 2009, 62: 84-88. 10.1136/jcp.2008.058339.PubMedCentralCrossRefPubMed Siebolts U, Varnholt H, Drebber U, Dienes HP, Wickenhauser C, Odenthal M: Tissues from routine pathology archives are suitable for microRNA analyses by quantitative PCR. J Clin Pathol. 2009, 62: 84-88. 10.1136/jcp.2008.058339.PubMedCentralCrossRefPubMed
27.
go back to reference Nonn L, Vaishnav A, Gallagher L, Gann PH: mRNA and micro-RNA expression analysis in laser-capture microdissected prostate biopsies: valuable tool for risk assessment and prevention trials. Exp Mol Pathol. 2010, 88: 45-51. 10.1016/j.yexmp.2009.10.005.PubMedCentralCrossRefPubMed Nonn L, Vaishnav A, Gallagher L, Gann PH: mRNA and micro-RNA expression analysis in laser-capture microdissected prostate biopsies: valuable tool for risk assessment and prevention trials. Exp Mol Pathol. 2010, 88: 45-51. 10.1016/j.yexmp.2009.10.005.PubMedCentralCrossRefPubMed
28.
go back to reference Noutsias M, Rohde M, Block A, Klippert K, Lettau O, Blunert K, Hummel M, Kühl U, Lehmkuhl H, Hetzer R, Rauch U, Poller W, Pauschinger M, Schultheiss HP, Volk HD, Kotsch K: Preamplification techniques for real-time RT-PCR analyses of endomyocardial biopsies. BMC Mol Biol. 2008, 9: 3-10.1186/1471-2199-9-3.PubMedCentralCrossRefPubMed Noutsias M, Rohde M, Block A, Klippert K, Lettau O, Blunert K, Hummel M, Kühl U, Lehmkuhl H, Hetzer R, Rauch U, Poller W, Pauschinger M, Schultheiss HP, Volk HD, Kotsch K: Preamplification techniques for real-time RT-PCR analyses of endomyocardial biopsies. BMC Mol Biol. 2008, 9: 3-10.1186/1471-2199-9-3.PubMedCentralCrossRefPubMed
30.
go back to reference Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3: 34.1-34.12.CrossRef Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3: 34.1-34.12.CrossRef
31.
go back to reference Mestdagh P, Van Vlierberghe P, De Weer A, Muth D, Westermann F, Speleman F, Vandesompele J: A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 2009, 10: R64-10.1186/gb-2009-10-6-r64.PubMedCentralCrossRefPubMed Mestdagh P, Van Vlierberghe P, De Weer A, Muth D, Westermann F, Speleman F, Vandesompele J: A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 2009, 10: R64-10.1186/gb-2009-10-6-r64.PubMedCentralCrossRefPubMed
32.
go back to reference R Development Core Team: R: A language and environment for statistical computing. 2011, R Foundation for Statistical Computing, Vienna, Austria, ISBN 3-900051-07-0, [http://www.R-project.org/] R Development Core Team: R: A language and environment for statistical computing. 2011, R Foundation for Statistical Computing, Vienna, Austria, ISBN 3-900051-07-0, [http://​www.​R-project.​org/​]
33.
go back to reference Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001, 29: 2002-2007.CrossRef Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001, 29: 2002-2007.CrossRef
34.
go back to reference O'Riordan JM, Abdel-latif MM, Ravi N, McNamara D, Byrne PJ, McDonald GS, Keeling PW, Kelleher D, Reynolds JV: Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Gastroenterol. 2005, 100: 1257-1264. 10.1111/j.1572-0241.2005.41338.x.CrossRefPubMed O'Riordan JM, Abdel-latif MM, Ravi N, McNamara D, Byrne PJ, McDonald GS, Keeling PW, Kelleher D, Reynolds JV: Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Gastroenterol. 2005, 100: 1257-1264. 10.1111/j.1572-0241.2005.41338.x.CrossRefPubMed
35.
go back to reference Colleypriest BJ, Ward SG, Tosh D: How does inflammation cause Barrett's metaplasia?. Curr Opin Pharmacol. 2009, 9: 721-726. 10.1016/j.coph.2009.09.005.CrossRefPubMed Colleypriest BJ, Ward SG, Tosh D: How does inflammation cause Barrett's metaplasia?. Curr Opin Pharmacol. 2009, 9: 721-726. 10.1016/j.coph.2009.09.005.CrossRefPubMed
36.
go back to reference Burgess JN, Payne WS, Andersen HA, Weiland LH, Carlson HC: Barrett esophagus: the columnar-epithelial-lined lower esophagus. Mayo Clin Proc. 1971, 46: 728-734.PubMed Burgess JN, Payne WS, Andersen HA, Weiland LH, Carlson HC: Barrett esophagus: the columnar-epithelial-lined lower esophagus. Mayo Clin Proc. 1971, 46: 728-734.PubMed
37.
go back to reference Szafranska AE, Doleshal M, Edmunds HS, Gordon S, Luttges J, Munding JB, Barth RJ, Gutmann EJ, Suriawinata AA, Marc Pipas J, Tannapfel A, Korc M, Hahn SA, Labourier E, Tsongalis GJ: Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues. Clin Chem. 2008, 54: 1716-1724. 10.1373/clinchem.2008.109603.PubMedCentralCrossRefPubMed Szafranska AE, Doleshal M, Edmunds HS, Gordon S, Luttges J, Munding JB, Barth RJ, Gutmann EJ, Suriawinata AA, Marc Pipas J, Tannapfel A, Korc M, Hahn SA, Labourier E, Tsongalis GJ: Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues. Clin Chem. 2008, 54: 1716-1724. 10.1373/clinchem.2008.109603.PubMedCentralCrossRefPubMed
38.
go back to reference Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007, 297: 1901-1908. 10.1001/jama.297.17.1901.CrossRefPubMed Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007, 297: 1901-1908. 10.1001/jama.297.17.1901.CrossRefPubMed
39.
go back to reference Kumarswamy R, Volkmann I, Thum T: Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011, 8: 1-8. 10.4161/rna.8.1.15302.CrossRef Kumarswamy R, Volkmann I, Thum T: Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011, 8: 1-8. 10.4161/rna.8.1.15302.CrossRef
40.
go back to reference Saini S, Majid S, Yamamura S, Tabatabai ZL, Suh SO, Shahryari V, Chen Y, Deng G, Tanaka Y, Dahiya R: Regulatory role of miR-203 in prostate cancer progression and metastasis. Clin Cancer Res. 2011, 17: 5287-5298. 10.1158/1078-0432.CCR-10-2619.CrossRefPubMed Saini S, Majid S, Yamamura S, Tabatabai ZL, Suh SO, Shahryari V, Chen Y, Deng G, Tanaka Y, Dahiya R: Regulatory role of miR-203 in prostate cancer progression and metastasis. Clin Cancer Res. 2011, 17: 5287-5298. 10.1158/1078-0432.CCR-10-2619.CrossRefPubMed
Metadata
Title
Changes of microRNAs-192, 196a and 203 correlate with Barrett's esophagus diagnosis and its progression compared to normal healthy individuals
Authors
Pavla Luzna
Jan Gregar
Ivo Uberall
Lenka Radova
Vlastimil Prochazka
Jiri Ehrmann Jr
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2011
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-6-114

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