MicroRNA (miRNA) Microarray Analysis in Well-Differentiated (WD) and Dedifferentiated (DD) Liposarcomas (LP)
PJ Zhang, D Baldwin, G Xu, AH Liu, D Gustafson, J Tobias, F Barr. University of Pennsylvania, Philadelphia
Background: The function of a microRNA is to silence multiple target genes. Depending upon its target genes, miRNA can function to promote or suppress cell growth. Abnormal miRNA expression has been shown in various tumors including liposarcomas. We hypothesize some miRNA's are expressed differentially in WD and DD LP and that these miRNA's may be useful in identifying subtle features of dedifferentiation in a WD LP.
Design: 18 paraffin blocks with WD (n10) or DD (8) histology were retrieved from 5 WD LP and 6 DD LP. Area of WD morphology was also obtained in 4 of 6 DD LP. Total RNA was extracted from 4 x 20 μm sections for Exiqon miRNA microarrays. A pooled sample from all samples was used as common reference. Data was analyzed with SAM and Partek software to identify differentially expressed miRNAs. qRT-PCR was performed to validate selected miRNA's in the same samples.
Results: Variable numbers of human miRNA's were found to be expressed differentially between DD LP (n=6) and WD LP (n=5); tissue with DD histology (n=8) and WD histology (n=10); tissue with WD histology from DD LP (n=4) and WD LP (n=5). The down regulation of miR-539 in tissue with DD histology and miR-193a-5p in WD area from DD LP was validated by qRT-PCR.
Conclusions: The expression of specific miRNAs is different in DD LP (regardless of samples containing DD or WD histology in these tumors) compared to WD LP. Different gene expression in WD tissue from DD LP and pure WD LP has also been reported in cDNA microarray analysis.These findings suggest a role of these miRNAs in progression of LP and change in miRNA expression can occur even before or without histologic dedifferentiation. The results of this study need to be further validated in larger tumor sets. The validated results can provide guidance to identify candidate genes functioning as oncogenes or tumor suppressors in LP, and subsequently potential targets for treatment and markers for early prediction of dedifferentiation in LP.
Category: Bone & Soft Tissue
Monday, March 22, 2010 1:00 PM
Poster Session II # 14, Monday Afternoon