Abstract | CONTEXT: While global microRNA ( miRNA) expression patterns of many embryologic, physiologic, and oncogenic processes have been described, description of the role of miRNAs in ductal adenocarcinoma of the pancreas is lacking. OBJECTIVE: DESIGN AND SETTING: MAIN OUTCOME MEASURES: Identification of differentially expressed miRNAs that could differentiate pancreatic cancer from normal pancreas, chronic pancreatitis, or both, as well as a pattern of miRNA expression predictive of long-term (>24 months) survival. Significance of Analysis of Microarrays and Prediction of Analysis of Microarrays were undertaken to identify miRNAs predictive of tissue type and prognosis. P values were calculated by t test, adjusted for multiple testing. Kaplan-Meier survival curves were constructed using mean miRNA expression (high vs low) as threshold and compared by log-rank analysis. RESULTS: Twenty-one miRNAs with increased expression and 4 with decreased expression were identified that correctly differentiated pancreatic cancer from benign pancreatic tissue in 90% of samples by cross validation. Fifteen overexpressed and 8 underexpressed miRNAs differentiated pancreatic cancer from chronic pancreatitis with 93% accuracy. A subgroup of 6 miRNAs was able to distinguish long-term survivors with node-positive disease from those dying within 24 months. Finally, high expression of miR-196a-2 was found to predict poor survival (median, 14.3 months [95% confidence interval, 12.4-16.2] vs 26.5 months [95% confidence interval, 23.4-29.6]; P = .009). CONCLUSIONS:
Pancreatic cancer may have a distinct miRNA expression pattern that may differentiate it from normal pancreas and chronic pancreatitis. miRNA expression patterns may be able to distinguish between long- and short-term survivors, but these findings need to be validated in other study populations.
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Authors | Mark Bloomston, Wendy L Frankel, Fabio Petrocca, Stefano Volinia, Hansjuerg Alder, John P Hagan, Chang-Gong Liu, Darshna Bhatt, Cristian Taccioli, Carlo M Croce |
Journal | JAMA
(JAMA)
Vol. 297
Issue 17
Pg. 1901-8
(May 02 2007)
ISSN: 1538-3598 [Electronic] United States |
PMID | 17473300
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Genetic Markers
- MicroRNAs
- RNA, Neoplasm
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Topics |
- Blotting, Northern
- Carcinoma, Pancreatic Ductal
(genetics)
- Genetic Markers
- Humans
- Immunohistochemistry
- Kaplan-Meier Estimate
- MicroRNAs
(analysis)
- Oligonucleotide Array Sequence Analysis
- Pancreas
(anatomy & histology, chemistry)
- Pancreatic Neoplasms
(genetics, mortality, pathology)
- Pancreatitis, Chronic
(genetics, pathology)
- Polymerase Chain Reaction
- Prognosis
- RNA, Neoplasm
(analysis)
- Tissue Array Analysis
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