MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma

Meir Preis, Timothy B. Gardner, Stuart R. Gordon, J. Marc Pipas, Todd A. Mackenzie, Erin E. Klein, Daniel S. Longnecker, Edward J. Gutmann, Lorenzo F. Sempere, Murray Korc

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Diagnosis and management of PDAC are hampered by the absence of sensitive and specific disease biomarkers. MicroRNAs (miRNA) are noncoding regulatory RNAs involved in initiation and progression of human cancers. In this study, we sought to determine whether miR-10b could serve as a biomarker for PDAC. Experimental Design: miRNA expression was characterized by fluorescence-based in situ hybridization using locked nucleic acid-modified DNA probes against miR-10b, miR-21, miR-155, miR-196a, and miR- 210, followed by codetection of proteins by immunohistochemistry on the same tissue sections. miRNA expression in surgically resected PDAC tissues and in endoscopic ultrasonography (EUS)-guided fine-needle aspirate (EUS-FNA) samples was analyzed in cytokeratin 19 (CK19)-positive epithelial cells using optical intensity analysis. Results: In 10 resected PDAC samples, miR-10b was the most frequently and consistently overexpressed miRNA among characterized miRNAs, exhibiting a four-fold increase in the cancer cells (P = 0.012). Given this preferential overexpression of miR-10b, we sought to determine whether miR-10b expression was clinically relevant. Accordingly, miR-10b expression was examined in 106 EUS-FNA samples obtained from pancreatic lesions. miR-10b expression was increased in cancer cells compared with CK19-positive epithelial cells in benign lesions (P = 0.0001). In patients with PDACs, lower levels of miR-10b were associated with improved response to multimodality neoadjuvant therapy, likelihood of surgical resection, delayed time to metastasis, and increased survival. Conclusion: miR-10b is a novel diagnostic biomarker for PDACs when assessing pancreatic lesions. Expression of miR-10b is predictive of response to neoadjuvant therapy and outcome in this disease.

Original languageEnglish (US)
Pages (from-to)5812-5821
Number of pages10
JournalClinical Cancer Research
Volume17
Issue number17
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Fingerprint

Neoadjuvant Therapy
MicroRNAs
Adenocarcinoma
Survival
Keratin-19
Endosonography
Biomarkers
Neoplasms
Epithelial Cells
Untranslated RNA
DNA Probes
Fluorescence In Situ Hybridization
Needles
Research Design
Immunohistochemistry
Neoplasm Metastasis
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Preis, M., Gardner, T. B., Gordon, S. R., Pipas, J. M., Mackenzie, T. A., Klein, E. E., ... Korc, M. (2011). MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. Clinical Cancer Research, 17(17), 5812-5821. https://doi.org/10.1158/1078-0432.CCR-11-0695

MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. / Preis, Meir; Gardner, Timothy B.; Gordon, Stuart R.; Pipas, J. Marc; Mackenzie, Todd A.; Klein, Erin E.; Longnecker, Daniel S.; Gutmann, Edward J.; Sempere, Lorenzo F.; Korc, Murray.

In: Clinical Cancer Research, Vol. 17, No. 17, 01.09.2011, p. 5812-5821.

Research output: Contribution to journalArticle

Preis, M, Gardner, TB, Gordon, SR, Pipas, JM, Mackenzie, TA, Klein, EE, Longnecker, DS, Gutmann, EJ, Sempere, LF & Korc, M 2011, 'MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma', Clinical Cancer Research, vol. 17, no. 17, pp. 5812-5821. https://doi.org/10.1158/1078-0432.CCR-11-0695
Preis, Meir ; Gardner, Timothy B. ; Gordon, Stuart R. ; Pipas, J. Marc ; Mackenzie, Todd A. ; Klein, Erin E. ; Longnecker, Daniel S. ; Gutmann, Edward J. ; Sempere, Lorenzo F. ; Korc, Murray. / MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 17. pp. 5812-5821.
@article{649bb79e5518421ba650f929faab0277,
title = "MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma",
abstract = "Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Diagnosis and management of PDAC are hampered by the absence of sensitive and specific disease biomarkers. MicroRNAs (miRNA) are noncoding regulatory RNAs involved in initiation and progression of human cancers. In this study, we sought to determine whether miR-10b could serve as a biomarker for PDAC. Experimental Design: miRNA expression was characterized by fluorescence-based in situ hybridization using locked nucleic acid-modified DNA probes against miR-10b, miR-21, miR-155, miR-196a, and miR- 210, followed by codetection of proteins by immunohistochemistry on the same tissue sections. miRNA expression in surgically resected PDAC tissues and in endoscopic ultrasonography (EUS)-guided fine-needle aspirate (EUS-FNA) samples was analyzed in cytokeratin 19 (CK19)-positive epithelial cells using optical intensity analysis. Results: In 10 resected PDAC samples, miR-10b was the most frequently and consistently overexpressed miRNA among characterized miRNAs, exhibiting a four-fold increase in the cancer cells (P = 0.012). Given this preferential overexpression of miR-10b, we sought to determine whether miR-10b expression was clinically relevant. Accordingly, miR-10b expression was examined in 106 EUS-FNA samples obtained from pancreatic lesions. miR-10b expression was increased in cancer cells compared with CK19-positive epithelial cells in benign lesions (P = 0.0001). In patients with PDACs, lower levels of miR-10b were associated with improved response to multimodality neoadjuvant therapy, likelihood of surgical resection, delayed time to metastasis, and increased survival. Conclusion: miR-10b is a novel diagnostic biomarker for PDACs when assessing pancreatic lesions. Expression of miR-10b is predictive of response to neoadjuvant therapy and outcome in this disease.",
author = "Meir Preis and Gardner, {Timothy B.} and Gordon, {Stuart R.} and Pipas, {J. Marc} and Mackenzie, {Todd A.} and Klein, {Erin E.} and Longnecker, {Daniel S.} and Gutmann, {Edward J.} and Sempere, {Lorenzo F.} and Murray Korc",
year = "2011",
month = "9",
day = "1",
doi = "10.1158/1078-0432.CCR-11-0695",
language = "English (US)",
volume = "17",
pages = "5812--5821",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "17",

}

TY - JOUR

T1 - MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma

AU - Preis, Meir

AU - Gardner, Timothy B.

AU - Gordon, Stuart R.

AU - Pipas, J. Marc

AU - Mackenzie, Todd A.

AU - Klein, Erin E.

AU - Longnecker, Daniel S.

AU - Gutmann, Edward J.

AU - Sempere, Lorenzo F.

AU - Korc, Murray

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Diagnosis and management of PDAC are hampered by the absence of sensitive and specific disease biomarkers. MicroRNAs (miRNA) are noncoding regulatory RNAs involved in initiation and progression of human cancers. In this study, we sought to determine whether miR-10b could serve as a biomarker for PDAC. Experimental Design: miRNA expression was characterized by fluorescence-based in situ hybridization using locked nucleic acid-modified DNA probes against miR-10b, miR-21, miR-155, miR-196a, and miR- 210, followed by codetection of proteins by immunohistochemistry on the same tissue sections. miRNA expression in surgically resected PDAC tissues and in endoscopic ultrasonography (EUS)-guided fine-needle aspirate (EUS-FNA) samples was analyzed in cytokeratin 19 (CK19)-positive epithelial cells using optical intensity analysis. Results: In 10 resected PDAC samples, miR-10b was the most frequently and consistently overexpressed miRNA among characterized miRNAs, exhibiting a four-fold increase in the cancer cells (P = 0.012). Given this preferential overexpression of miR-10b, we sought to determine whether miR-10b expression was clinically relevant. Accordingly, miR-10b expression was examined in 106 EUS-FNA samples obtained from pancreatic lesions. miR-10b expression was increased in cancer cells compared with CK19-positive epithelial cells in benign lesions (P = 0.0001). In patients with PDACs, lower levels of miR-10b were associated with improved response to multimodality neoadjuvant therapy, likelihood of surgical resection, delayed time to metastasis, and increased survival. Conclusion: miR-10b is a novel diagnostic biomarker for PDACs when assessing pancreatic lesions. Expression of miR-10b is predictive of response to neoadjuvant therapy and outcome in this disease.

AB - Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Diagnosis and management of PDAC are hampered by the absence of sensitive and specific disease biomarkers. MicroRNAs (miRNA) are noncoding regulatory RNAs involved in initiation and progression of human cancers. In this study, we sought to determine whether miR-10b could serve as a biomarker for PDAC. Experimental Design: miRNA expression was characterized by fluorescence-based in situ hybridization using locked nucleic acid-modified DNA probes against miR-10b, miR-21, miR-155, miR-196a, and miR- 210, followed by codetection of proteins by immunohistochemistry on the same tissue sections. miRNA expression in surgically resected PDAC tissues and in endoscopic ultrasonography (EUS)-guided fine-needle aspirate (EUS-FNA) samples was analyzed in cytokeratin 19 (CK19)-positive epithelial cells using optical intensity analysis. Results: In 10 resected PDAC samples, miR-10b was the most frequently and consistently overexpressed miRNA among characterized miRNAs, exhibiting a four-fold increase in the cancer cells (P = 0.012). Given this preferential overexpression of miR-10b, we sought to determine whether miR-10b expression was clinically relevant. Accordingly, miR-10b expression was examined in 106 EUS-FNA samples obtained from pancreatic lesions. miR-10b expression was increased in cancer cells compared with CK19-positive epithelial cells in benign lesions (P = 0.0001). In patients with PDACs, lower levels of miR-10b were associated with improved response to multimodality neoadjuvant therapy, likelihood of surgical resection, delayed time to metastasis, and increased survival. Conclusion: miR-10b is a novel diagnostic biomarker for PDACs when assessing pancreatic lesions. Expression of miR-10b is predictive of response to neoadjuvant therapy and outcome in this disease.

UR - http://www.scopus.com/inward/record.url?scp=80052445088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052445088&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-11-0695

DO - 10.1158/1078-0432.CCR-11-0695

M3 - Article

C2 - 21652542

AN - SCOPUS:80052445088

VL - 17

SP - 5812

EP - 5821

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 17

ER -