MicroRNA Expression Profiling Identifies Potential Prognostic Indicators in Primary Solitary Fibrous Tumors
Elizabeth G Demicco, Khalida Wani, Alexander J Lazar, Aldape D Kenneth, Wei-Lien Wang. Mount Sinai Medical Center, New York, NY; Universitiy of Texas MD Anderson Cancer Center, Houston, TX
Background: The behavior of solitary fibrous tumors is notoriously difficult to predict and reliable biomarkers are lacking. MicroRNA (miRNA) are non-coding RNAs with post-transcriptional regulatory functions, which have been implicated in tumorigenesis of a number of malignancies. Currently, the role of miRNA in primary solitary fibrous tumors (SFT) is poorly understood. We therefore sought to determine the expression patterns and prognostic value of miRNA in benign and malignant primary SFT.
Design: RNA was extracted from 18 formalin-fixed paraffin-embedded primary SFTs: 9 tumors that gave rise to metastases, and 9 tumors that did not. MiRNA expression profiling was performed using a real-time PCR based platform on a Taqman Human miRNA array card containing 378 annotated miRNAs. Expression was normalized to housekeeping miRNAs. Two sample t-tests were used on a probe-by-probe basis to compare malignant with benign tumors.
Results: The benign tumors had a median clinical follow-up of 100 (range 77-147) months, while the malignant tumors metastasized at a median of 30 (range, at presentation – 71) months. Sites included pleura (n=6), abdomen (n=6), and soft tissues of head, extremity, or trunk (n=6). Two sample t-tests between metastasizing and benign populations identified 9 differentially expressed miRNA with p-value <0.05. MiR-30c, miR-489, miR-886-3p, miR-142-3p, miR-597, mir-34c, miR-570, and miR-653 showed 1.6 to 18.4-fold reduction in expression in malignant SFT vs. benign, while miR-339-5p and miR-450b-5p had 14.7 to 24.9-fold increase in expression in malignant SFT.
Conclusions: We identified a subset of miRNA that differentiated between benign and malignant SFT in formalin fixed paraffin-embedded tissue. Several of these miRNAs have been previously identified as having tumor suppressor functions. In particular, miR-489, miR-30c, miR-34c and miR-886-3p have been shown to be downregulated in carcinogenesis. MiR-886-3p has been postulated to regulate focal adhesion pathways and DNA replication, while miR-489 has been suggested to play a role in cell growth and mesenchymal differentiation, and miR-34c and miR-30c may repress cell migration and invasion. In our population, these were downregulated in aggressive tumors, suggesting that they may function similarly in SFT. Network analysis and biomarker validation is ongoing.
Category: Bone & Soft Tissue
Monday, March 4, 2013 1:00 PM
Poster Session II # 19, Monday Afternoon