Differential MicroRNA Expression in Low-Grade and High-Grade Cartilaginous Tumors
Khalida Wani, Micheal Deavers, Kenneth Aldape, Alexander Lazar, Wei-Lien Wang. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Tumor grade is considered to be the most important prognostic indicator for cartilaginous tumors. However, as there is no univerally accepted grading system, traditional grading can be subjective. We sought to identify more objective markers using miRNA profiling in decalcified formalin-fixed paraffin embedded tissue.
Design: Twenty-nine cartilaginous tumors with decalcified FFPE tissue were identified. Low grade cartilaginous tumors (n=14) included enchondromas (n=5) and low grade chondrosarcomas (n=9). High-grade cartilaginous tumors (n=14) included high-grade chondrosarcomas (n=9) and dedifferentiated chondrosarcoma (n=5). MiRNA expression profiling was performed using a real-time PCR based platform on Taqman Human miRNA microfluidics cards which contain 378 annotated miRNAs. Differential fold change and the student t-test was used on a probe-by-probe basis to compare low-grade verse high-grade cartilaginous tumors.
Results: A set of 57 microRNAs were found to be differentially expressed between low-grade and high-grade tumors (p<0.05). 56 of these microRNAs were overexpressed in the high grade cartilaginous tumors while miR-486 was the only microRNA found to be highly expressed in the low grade cartilaginous tumors. Differential expressed miRNAs was also seen between enchondromas, low-grade Chs, high-grade Chs and dedifferentiated Chs.
Conclusions: Our studies indicate that microRNA analysis on decalcified formalin fixed paraffin embedded tissue shows promise as a useful tool for classifying cartilaginous tumors. We identified a set of microRNAs that are differentially expressed between high grade and low grade cartilaginous tumors. Several of the miRNAs overexpressed in the high grade tumors such as miR-21, miR-31, miR-221, miR-222 have been reported to be associated with poor prognosis in other malignancies. Among the reported mRNA targets of miR-21, are PTEN, PDCD4 and NF1B, suggesting a role for miR-21 in regulating apoptosis, proliferation and migration. In addition, low grade tumors had higher expression of miR-486, which is reported to act as tumor suppressor in gastric cancers, perhaps behaving in a similar function in cartilaginous tumors.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 11:45 AM
Proffered Papers: Section G, Tuesday Morning