Global microRNA profiling of pancreatic neuroendocrine neoplasias.
BACKGROUND
Pancreatic neuroendocrine neoplasms (pNEN) are rare tumors with a poor prognosis. Although increasing data have accumulated on the molecular pathology of pNEN, very scarce data exist on microRNAs in pNEN and no data are published on microRNAs as potential biomarkers of pNEN in serum. This study aimed to identify microRNA signatures of pNEN in tissue and serum.


METHODS
We included tissue samples from 37 patients with pNEN, 9 patients with non-neoplastic pancreatic pathology, seven samples of micro-dissected pancreatic islets and serum samples of 27 patients with pNEN, as well as of 15 healthy volunteers. MicroRNA expression profiles were established using real-time quantitative Polymerase Chain reaction (PCR) for 754 microRNAs.


RESULTS
MicroRNA signatures differed between pNEN, pancreatic islets and total pancreas, with virtually no overlap between the groups of de-regulated microRNAs. Expression of miR-642 correlated with Ki67 (MiB1) score and miR-210 correlated with metastatic disease. When comparing microRNA levels in serum from patients with pNEN and healthy volunteers, 13 microRNAs were more abundant in the serum of patients. MiR-193b was also up-regulated in pNEN tissue when compared to pancreatic islets and remained significantly increased in serum even when corrected for multiple testing.


CONCLUSIONS
Evaluation of microRNAs appears to be promising in the assessment of pNEN. In particular, miR-193b, which is also increased in serum, may be a potential new biomarker of pNEN.
Institut für Pathologie, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. christoph.thorns@uksh.de.
Chistoph
C
Thorns
Claudia
C
Schurmann
Niklas
N
Gebauer
Henri
H
Wallaschofski
Christiane
C
Kümpers
Veronica
V
Bernard
Alfred C
AC
Feller
Tobias
T
Keck
Jens K
JK
Habermann
Nehara
N
Begum
Hendrik
H
Lehnert
Georg
G
Brabant
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
D014408:Biomarkers, Tumor; D035683:MicroRNAs
Pancreatic neuroendocrine neoplasia; miR-193b; microRNA; serum