MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Roldo
Claudia
C
Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
Missiaglia
Edoardo
E
Hagan
John P
JP
Falconi
Massimo
M
Capelli
Paola
P
Bersani
Samantha
S
Calin
George Adrian
GA
Volinia
Stefano
S
Liu
Chang-Gong
CG
Scarpa
Aldo
A
Croce
Carlo M
CM
D018267:Carcinoma, Acinar Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D020869:Gene Expression Profiling; D006801:Humans; D007340:Insulinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008113:Liver Neoplasms / Q000556:secondary; D035683:MicroRNAs / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D013534:Survival
D035683:MicroRNAs