MicroRNA miR-155 is a biomarker of early pancreatic neoplasia

Nils Habbe, Jan Bart M Koorstra, Joshua T. Mendell, G. Johan Offerhaus, Kon Ryu Ji, Georg Feldmann, Michael E. Mullendore, Michael G. Goggins, Seung Mo Hong, Anirban Maitra

Research output: Contribution to journalArticle

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Abstract

Background: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions of pancreatic cancer. Misexpression of microRNAs (miRNAs) is commonly observed in pancreatic adenocarcinoma. In contrast, miRNA abnormalities in pancreatic cancer precursor lesions have not been documented. Experimental design: Relative expression levels of a panel of twelve miRNAs upregulated in pancreatic cancers were assessed in 15 non-invasive IPMNs, using quantitative reverse transcription PCR (qRT-PCR). Two significantly overexpressed miRNAs - miR-155 and miR-21 - were evaluated by locked nucleic acid in situ hybridization (LNA-ISH) in a panel of 64 archival IPMNs. The expression of miR-155 and miR-21 was also evaluated in pancreatic juice samples obtained from ten patients with surgically resected IPMNs and five patients with non-neoplastic pancreatobiliary disorders ("disease controls"). Results: Significant overexpression by qRT-PCR of ten of the twelve miRNAs was observed in the 15 IPMNs versus matched controls (p < 0.05), with miR-155 (mean 11.6-fold) and miR-21 (mean 12.1-fold) demonstrating highest relative fold-changes in the precursor lesions. LNA-ISH confirmed the expression of miR-155 in 53 of 64 (83%) IPMNs compared to 4 of 54 (7%) normal ducts, and of miR-21 in 52 of 64 (81%) IPMNs compared to 1 of 54 (2%) normal ducts, respectively (p < 0.0001). Upregulation of miR-155 transcripts by qRT-PCR was observed in 6 of 10 (60%) IPMN-associated pancreatic juice samples compared to 0 of 5 (0%) disease controls. Conclusions: Aberrant miRNA expression is an early event in the multistage progression of pancreatic cancer, and miR-155 warrants further evaluation as a biomarker for IPMNs in clinical samples.

Original languageEnglish (US)
Pages (from-to)340-346
Number of pages7
JournalCancer Biology and Therapy
Volume8
Issue number4
StatePublished - Feb 15 2009

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MicroRNAs
Biomarkers
Pancreatic Neoplasms
Neoplasms
Reverse Transcription
Pancreatic Juice
Polymerase Chain Reaction
In Situ Hybridization
Adenocarcinoma
Research Design
Up-Regulation

Keywords

  • Intraductal papillary mucinous neoplasm
  • microRNA
  • miR-155
  • Pancreatic cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Habbe, N., Koorstra, J. B. M., Mendell, J. T., Offerhaus, G. J., Ji, K. R., Feldmann, G., ... Maitra, A. (2009). MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biology and Therapy, 8(4), 340-346.

MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. / Habbe, Nils; Koorstra, Jan Bart M; Mendell, Joshua T.; Offerhaus, G. Johan; Ji, Kon Ryu; Feldmann, Georg; Mullendore, Michael E.; Goggins, Michael G.; Hong, Seung Mo; Maitra, Anirban.

In: Cancer Biology and Therapy, Vol. 8, No. 4, 15.02.2009, p. 340-346.

Research output: Contribution to journalArticle

Habbe, N, Koorstra, JBM, Mendell, JT, Offerhaus, GJ, Ji, KR, Feldmann, G, Mullendore, ME, Goggins, MG, Hong, SM & Maitra, A 2009, 'MicroRNA miR-155 is a biomarker of early pancreatic neoplasia', Cancer Biology and Therapy, vol. 8, no. 4, pp. 340-346.
Habbe N, Koorstra JBM, Mendell JT, Offerhaus GJ, Ji KR, Feldmann G et al. MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biology and Therapy. 2009 Feb 15;8(4):340-346.
Habbe, Nils ; Koorstra, Jan Bart M ; Mendell, Joshua T. ; Offerhaus, G. Johan ; Ji, Kon Ryu ; Feldmann, Georg ; Mullendore, Michael E. ; Goggins, Michael G. ; Hong, Seung Mo ; Maitra, Anirban. / MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. In: Cancer Biology and Therapy. 2009 ; Vol. 8, No. 4. pp. 340-346.
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abstract = "Background: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions of pancreatic cancer. Misexpression of microRNAs (miRNAs) is commonly observed in pancreatic adenocarcinoma. In contrast, miRNA abnormalities in pancreatic cancer precursor lesions have not been documented. Experimental design: Relative expression levels of a panel of twelve miRNAs upregulated in pancreatic cancers were assessed in 15 non-invasive IPMNs, using quantitative reverse transcription PCR (qRT-PCR). Two significantly overexpressed miRNAs - miR-155 and miR-21 - were evaluated by locked nucleic acid in situ hybridization (LNA-ISH) in a panel of 64 archival IPMNs. The expression of miR-155 and miR-21 was also evaluated in pancreatic juice samples obtained from ten patients with surgically resected IPMNs and five patients with non-neoplastic pancreatobiliary disorders ({"}disease controls{"}). Results: Significant overexpression by qRT-PCR of ten of the twelve miRNAs was observed in the 15 IPMNs versus matched controls (p < 0.05), with miR-155 (mean 11.6-fold) and miR-21 (mean 12.1-fold) demonstrating highest relative fold-changes in the precursor lesions. LNA-ISH confirmed the expression of miR-155 in 53 of 64 (83{\%}) IPMNs compared to 4 of 54 (7{\%}) normal ducts, and of miR-21 in 52 of 64 (81{\%}) IPMNs compared to 1 of 54 (2{\%}) normal ducts, respectively (p < 0.0001). Upregulation of miR-155 transcripts by qRT-PCR was observed in 6 of 10 (60{\%}) IPMN-associated pancreatic juice samples compared to 0 of 5 (0{\%}) disease controls. Conclusions: Aberrant miRNA expression is an early event in the multistage progression of pancreatic cancer, and miR-155 warrants further evaluation as a biomarker for IPMNs in clinical samples.",
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author = "Nils Habbe and Koorstra, {Jan Bart M} and Mendell, {Joshua T.} and Offerhaus, {G. Johan} and Ji, {Kon Ryu} and Georg Feldmann and Mullendore, {Michael E.} and Goggins, {Michael G.} and Hong, {Seung Mo} and Anirban Maitra",
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T1 - MicroRNA miR-155 is a biomarker of early pancreatic neoplasia

AU - Habbe, Nils

AU - Koorstra, Jan Bart M

AU - Mendell, Joshua T.

AU - Offerhaus, G. Johan

AU - Ji, Kon Ryu

AU - Feldmann, Georg

AU - Mullendore, Michael E.

AU - Goggins, Michael G.

AU - Hong, Seung Mo

AU - Maitra, Anirban

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N2 - Background: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions of pancreatic cancer. Misexpression of microRNAs (miRNAs) is commonly observed in pancreatic adenocarcinoma. In contrast, miRNA abnormalities in pancreatic cancer precursor lesions have not been documented. Experimental design: Relative expression levels of a panel of twelve miRNAs upregulated in pancreatic cancers were assessed in 15 non-invasive IPMNs, using quantitative reverse transcription PCR (qRT-PCR). Two significantly overexpressed miRNAs - miR-155 and miR-21 - were evaluated by locked nucleic acid in situ hybridization (LNA-ISH) in a panel of 64 archival IPMNs. The expression of miR-155 and miR-21 was also evaluated in pancreatic juice samples obtained from ten patients with surgically resected IPMNs and five patients with non-neoplastic pancreatobiliary disorders ("disease controls"). Results: Significant overexpression by qRT-PCR of ten of the twelve miRNAs was observed in the 15 IPMNs versus matched controls (p < 0.05), with miR-155 (mean 11.6-fold) and miR-21 (mean 12.1-fold) demonstrating highest relative fold-changes in the precursor lesions. LNA-ISH confirmed the expression of miR-155 in 53 of 64 (83%) IPMNs compared to 4 of 54 (7%) normal ducts, and of miR-21 in 52 of 64 (81%) IPMNs compared to 1 of 54 (2%) normal ducts, respectively (p < 0.0001). Upregulation of miR-155 transcripts by qRT-PCR was observed in 6 of 10 (60%) IPMN-associated pancreatic juice samples compared to 0 of 5 (0%) disease controls. Conclusions: Aberrant miRNA expression is an early event in the multistage progression of pancreatic cancer, and miR-155 warrants further evaluation as a biomarker for IPMNs in clinical samples.

AB - Background: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions of pancreatic cancer. Misexpression of microRNAs (miRNAs) is commonly observed in pancreatic adenocarcinoma. In contrast, miRNA abnormalities in pancreatic cancer precursor lesions have not been documented. Experimental design: Relative expression levels of a panel of twelve miRNAs upregulated in pancreatic cancers were assessed in 15 non-invasive IPMNs, using quantitative reverse transcription PCR (qRT-PCR). Two significantly overexpressed miRNAs - miR-155 and miR-21 - were evaluated by locked nucleic acid in situ hybridization (LNA-ISH) in a panel of 64 archival IPMNs. The expression of miR-155 and miR-21 was also evaluated in pancreatic juice samples obtained from ten patients with surgically resected IPMNs and five patients with non-neoplastic pancreatobiliary disorders ("disease controls"). Results: Significant overexpression by qRT-PCR of ten of the twelve miRNAs was observed in the 15 IPMNs versus matched controls (p < 0.05), with miR-155 (mean 11.6-fold) and miR-21 (mean 12.1-fold) demonstrating highest relative fold-changes in the precursor lesions. LNA-ISH confirmed the expression of miR-155 in 53 of 64 (83%) IPMNs compared to 4 of 54 (7%) normal ducts, and of miR-21 in 52 of 64 (81%) IPMNs compared to 1 of 54 (2%) normal ducts, respectively (p < 0.0001). Upregulation of miR-155 transcripts by qRT-PCR was observed in 6 of 10 (60%) IPMN-associated pancreatic juice samples compared to 0 of 5 (0%) disease controls. Conclusions: Aberrant miRNA expression is an early event in the multistage progression of pancreatic cancer, and miR-155 warrants further evaluation as a biomarker for IPMNs in clinical samples.

KW - Intraductal papillary mucinous neoplasm

KW - microRNA

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KW - Pancreatic cancer

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