Originally published as JCO Early Release 10.1200/JCO.2005.05.5194 on September 11 2006
Journal of Clinical Oncology, Vol 24, No 29 (October 10), 2006: pp. 4677-4684
© 2006 American Society of Clinical Oncology.
MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors Are Associated With Distinctive Pathologic Features and Clinical Behavior
Claudia Roldo,
Edoardo Missiaglia,
John P. Hagan,
Massimo Falconi,
Paola Capelli,
Samantha Bersani,
George Adrian Calin,
Stefano Volinia,
Chang-Gong Liu,
Aldo Scarpa,
Carlo M. Croce
From the Departments of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH; Departments of Pathology and Surgical and Gastroenterological Sciences, Università di Verona, Verona; and the Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy
Address reprint requests in the United States to Carlo M. Croce, MD, Ohio State University, Comprehensive Cancer Center, Wiseman Hall Room 385K, 410 W 12th Ave, Columbus, OH; e-mail: Carlo.Croce{at}osumc.edu; and in Europe to Aldo Scarpa, MD, Verona University, strada Le grazie 8, 37134 Verona, Italy; e-mail: aldo.scarpa{at}univr.it
PURPOSE: We investigated the global microRNA expression patterns in normal pancreas, pancreatic endocrine tumors and acinar carcinomas to evaluate their involvement in transformation and malignant progression of these tumor types. MicroRNAs are small noncoding RNAs that regulate gene expression by targeting specific mRNAs for degradation or translation inhibition. Recent evidence indicates that microRNAs can contribute to tumor development and progression and may have diagnostic and prognostic value in several human malignancies.
MATERIALS AND METHODS: Using a custom microarray, we studied the global microRNA expression in 12 nontumor pancreas and 44 pancreatic primary tumors, including 12 insulinomas, 28 nonfunctioning endocrine tumors, and four acinar carcinomas.
RESULTS: Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis.
CONCLUSION: These results suggest that alteration in microRNA expression is related to endocrine and acinar neoplastic transformation and progression of malignancy, and might prove useful in distinguishing tumors with different clinical behavior.
published online ahead of print at www.jco.org on September 11, 2006.
Supported by Program Project Grants No. P01CA76259 and P01CA81534 from the National Cancer Institute (C.M.C.), by a Kimmel Scholar award (G.A.C.), Associazione Italiana Ricerca Cancro (AIRC; A.S.), Milan, Italy; Fondazione Cassa di Risparmio di Verona (Bando 2005), Italy; Ministeri Università e Salute, Rome, Italy; European Community Grant No. PL018771; and Fondazione Giorgio Zanotto, Verona, Italy.
C.R. and E.M. contributed equally to this work. A.S. and C.M.C. contributed equally to this work.
Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
P. Olson, J. Lu, H. Zhang, A. Shai, M. G. Chun, Y. Wang, S. K. Libutti, E. K. Nakakura, T. R. Golub, and D. Hanahan
MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer
Genes & Dev.,
September 15, 2009;
23(18):
2152 - 2165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Tombol, P. M Szabo, V. Molnar, Z. Wiener, G. Tolgyesi, J. Horanyi, P. Riesz, P. Reismann, A. Patocs, I. Liko, et al.
Integrative molecular bioinformatics study of human adrenocortical tumors: microRNA, tissue-specific target prediction, and pathway analysis
Endocr. Relat. Cancer,
September 1, 2009;
16(3):
895 - 906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wang, J. Chen, P. Chang, A. LeBlanc, D. Li, J. L. Abbruzzesse, M. L. Frazier, A. M. Killary, and S. Sen
MicroRNAs in Plasma of Pancreatic Ductal Adenocarcinoma Patients as Novel Blood-Based Biomarkers of Disease
Cancer Prevention Research,
September 1, 2009;
2(9):
807 - 813.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Sotiropoulou, G. Pampalakis, E. Lianidou, and Z. Mourelatos
Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell
RNA,
August 1, 2009;
15(8):
1443 - 1461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kato, L. Arce, and R. Natarajan
MicroRNAs and Their Role in Progressive Kidney Diseases
Clin. J. Am. Soc. Nephrol.,
July 1, 2009;
4(7):
1255 - 1266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Yamamichi, R. Shimomura, K.-i. Inada, K. Sakurai, T. Haraguchi, Y. Ozaki, S. Fujita, T. Mizutani, C. Furukawa, M. Fujishiro, et al.
Locked Nucleic Acid In situ Hybridization Analysis of miR-21 Expression during Colorectal Cancer Development
Clin. Cancer Res.,
June 15, 2009;
15(12):
4009 - 4016.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Vacca and F. Dammacco
MicroRNAs to know in Waldenstrom macroglobulinemia
Blood,
April 30, 2009;
113(18):
4133 - 4134.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Roccaro, A. Sacco, C. Chen, J. Runnels, X. Leleu, F. Azab, A. K. Azab, X. Jia, H. T. Ngo, M. R. Melhem, et al.
microRNA expression in the biology, prognosis, and therapy of Waldenstrom macroglobulinemia
Blood,
April 30, 2009;
113(18):
4391 - 4402.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sun, Q. Wang, S. Balk, M. Brown, G.-S. M. Lee, and P. Kantoff
The Role of microRNA-221 and microRNA-222 in Androgen-Independent Prostate Cancer Cell Lines
Cancer Res.,
April 15, 2009;
69(8):
3356 - 3363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Bandres, N. Bitarte, F. Arias, J. Agorreta, P. Fortes, X. Agirre, R. Zarate, J. A. Diaz-Gonzalez, N. Ramirez, J. J. Sola, et al.
microRNA-451 Regulates Macrophage Migration Inhibitory Factor Production and Proliferation of Gastrointestinal Cancer Cells
Clin. Cancer Res.,
April 1, 2009;
15(7):
2281 - 2290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Hiyoshi, H. Kamohara, R. Karashima, N. Sato, Y. Imamura, Y. Nagai, N. Yoshida, E. Toyama, N. Hayashi, M. Watanabe, et al.
MicroRNA-21 Regulates the Proliferation and Invasion in Esophageal Squamous Cell Carcinoma
Clin. Cancer Res.,
March 15, 2009;
15(6):
1915 - 1922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. E.W. Cohen, H. Zhu, M. W. Lingen, L. E. Martin, W.-L. Kuo, E. A. Choi, M. Kocherginsky, J. S. Parker, C. H. Chung, and M. R. Rosner
A Feed-Forward Loop Involving Protein Kinase C{alpha} and MicroRNAs Regulates Tumor Cell Cycle
Cancer Res.,
January 1, 2009;
69(1):
65 - 74.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Toloubeydokhti, Qun Pan, Xiaoping Luo, O. Bukulmez, and N. Chegini
The Expression and Ovarian Steroid Regulation of Endometrial Micro-RNAs
Reproductive Sciences,
December 1, 2008;
15(10):
993 - 1001.
[Abstract]
[PDF]
|
|
|
|
|
|
|
X. Agirre, A. Jimenez-Velasco, E. San Jose-Eneriz, L. Garate, E. Bandres, L. Cordeu, O. Aparicio, B. Saez, G. Navarro, A. Vilas-Zornoza, et al.
Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth
Mol. Cancer Res.,
December 1, 2008;
6(12):
1830 - 1840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K.-W. Chang, C.-J. Liu, T.-H. Chu, H.-W. Cheng, P.-S. Hung, W.-Y. Hu, and S.-C. Lin
Association between High miR-211 microRNA Expression and the Poor Prognosis of Oral Carcinoma
Journal of Dental Research,
November 1, 2008;
87(11):
1063 - 1068.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L.-X. Yan, X.-F. Huang, Q. Shao, M.-Y. Huang, L. Deng, Q.-L. Wu, Y.-X. Zeng, and J.-Y. Shao
MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis
RNA,
November 1, 2008;
14(11):
2348 - 2360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. G. de Yebenes, L. Belver, D. G. Pisano, S. Gonzalez, A. Villasante, C. Croce, L. He, and A. R. Ramiro
miR-181b negatively regulates activation-induced cytidine deaminase in B cells
J. Exp. Med.,
September 29, 2008;
205(10):
2199 - 2206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-W. Lee, C. H. Choi, J.-J. Choi, Y.-A. Park, S.-J. Kim, S. Y. Hwang, W. Y. Kim, T.-J. Kim, J.-H. Lee, B.-G. Kim, et al.
Altered MicroRNA Expression in Cervical Carcinomas
Clin. Cancer Res.,
May 1, 2008;
14(9):
2535 - 2542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Nam, H. Yoon, S. W. Kim, H. Kim, Y. T. Kim, J. H. Kim, J. W. Kim, and S. Kim
MicroRNA Expression Profiles in Serous Ovarian Carcinoma
Clin. Cancer Res.,
May 1, 2008;
14(9):
2690 - 2695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Zhang
MicroRNomics: a newly emerging approach for disease biology
Physiol Genomics,
April 1, 2008;
33(2):
139 - 147.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-X. Wang, B. W. Rajeev, A. J. Stromberg, N. Ren, G. Tang, Q. Huang, I. Rigoutsos, and P. T. Nelson
The Expression of MicroRNA miR-107 Decreases Early in Alzheimer's Disease and May Accelerate Disease Progression through Regulation of {beta}-Site Amyloid Precursor Protein-Cleaving Enzyme 1
J. Neurosci.,
January 30, 2008;
28(5):
1213 - 1223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yang, W. Kong, L. He, J.-J. Zhao, J. D. O'Donnell, J. Wang, R. M. Wenham, D. Coppola, P. A. Kruk, S. V. Nicosia, et al.
MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN
Cancer Res.,
January 15, 2008;
68(2):
425 - 433.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Jiang, Y. Gusev, I. Aderca, T. A. Mettler, D. M. Nagorney, D. J. Brackett, L. R. Roberts, and T. D. Schmittgen
Association of MicroRNA Expression in Hepatocellular Carcinomas with Hepatitis Infection, Cirrhosis, and Patient Survival
Clin. Cancer Res.,
January 15, 2008;
14(2):
419 - 427.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Frankel, N. R. Christoffersen, A. Jacobsen, M. Lindow, A. Krogh, and A. H. Lund
Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells
J. Biol. Chem.,
January 11, 2008;
283(2):
1026 - 1033.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Guo, Z. Chen, L. Zhang, F. Zhou, S. Shi, X. Feng, B. Li, X. Meng, X. Ma, M. Luo, et al.
Distinctive MicroRNA Profiles Relating to Patient Survival in Esophageal Squamous Cell Carcinoma
Cancer Res.,
January 1, 2008;
68(1):
26 - 33.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Pan, X. Luo, T. Toloubeydokhti, and N. Chegini
The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression
Mol. Hum. Reprod.,
November 1, 2007;
13(11):
797 - 806.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. Corsten, R. Miranda, R. Kasmieh, A. M. Krichevsky, R. Weissleder, and K. Shah
MicroRNA-21 Knockdown Disrupts Glioma Growth In vivo and Displays Synergistic Cytotoxicity with Neural Precursor Cell Delivered S-TRAIL in Human Gliomas
Cancer Res.,
October 1, 2007;
67(19):
8994 - 9000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. Iorio, R. Visone, G. Di Leva, V. Donati, F. Petrocca, P. Casalini, C. Taccioli, S. Volinia, C.-G. Liu, H. Alder, et al.
MicroRNA Signatures in Human Ovarian Cancer
Cancer Res.,
September 15, 2007;
67(18):
8699 - 8707.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Berkhout and K.-T. Jeang
RISCy Business: MicroRNAs, Pathogenesis, and Viruses
J. Biol. Chem.,
September 14, 2007;
282(37):
26641 - 26645.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zhang, J. E. Dahlberg, and W. Tam
MicroRNAs in Tumorigenesis: A Primer
Am. J. Pathol.,
September 1, 2007;
171(3):
728 - 738.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-O. Lui, N. Pourmand, B. K. Patterson, and A. Fire
Patterns of Known and Novel Small RNAs in Human Cervical Cancer
Cancer Res.,
July 1, 2007;
67(13):
6031 - 6043.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. P. Porkka, M. J. Pfeiffer, K. K. Waltering, R. L. Vessella, T. L.J. Tammela, and T. Visakorpi
MicroRNA Expression Profiling in Prostate Cancer
Cancer Res.,
July 1, 2007;
67(13):
6130 - 6135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Negrini, M. Ferracin, S. Sabbioni, and C. M. Croce
MicroRNAs in human cancer: from research to therapy
J. Cell Sci.,
June 1, 2007;
120(11):
1833 - 1840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhu, M.-L. Si, H. Wu, and Y.-Y. Mo
MicroRNA-21 Targets the Tumor Suppressor Gene Tropomyosin 1 (TPM1)
J. Biol. Chem.,
May 11, 2007;
282(19):
14328 - 14336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bloomston, W. L. Frankel, F. Petrocca, S. Volinia, H. Alder, J. P. Hagan, C.-G. Liu, D. Bhatt, C. Taccioli, and C. M. Croce
MicroRNA Expression Patterns to Differentiate Pancreatic Adenocarcinoma From Normal Pancreas and Chronic Pancreatitis
JAMA,
May 2, 2007;
297(17):
1901 - 1908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Waldman and A. Terzic
Translating MicroRNA Discovery Into Clinical Biomarkers in Cancer
JAMA,
May 2, 2007;
297(17):
1923 - 1925.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Blenkiron and E. A. Miska
miRNAs in cancer: approaches, aetiology, diagnostics and therapy
Hum. Mol. Genet.,
April 15, 2007;
16(R1):
R106 - R113.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. van Rooij, L. B. Sutherland, N. Liu, A. H. Williams, J. McAnally, R. D. Gerard, J. A. Richardson, and E. N. Olson
A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure
PNAS,
November 28, 2006;
103(48):
18255 - 18260.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
