title: A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas.
abstract: Sarcomas are malignant heterogenous tumors of mesenchymal derivation. Emerging data suggest that miRNA might have a causal role in sarcomagenesis. Herein, we used a selective miRNA screening platform to study the comparative global miRNA expression signatures in a cohort of human sarcomas with the caveat that comparisons between tumor and non-tumor cells were performed from the same patients using formalin-fixed paraffin-embedded tissue. Five histologic types were examined that included: myxoid liposarcoma, well-differentiated liposarcoma, dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, and synovial sarcoma. In addition, soft-tissue lipomas and normal fat were included as a separate set of controls for the lipogenic tumors. Clustering analysis showed a distinct global difference in expression patterns between the normal and sarcoma tissues. Expression signatures in an unsupervised hierarchical clustering analysis revealed tight clustering in synovial and myxoid liposarcomas, and the least clustering was observed in the pleomorphic rhabdomyosarcoma subtype. MiR-145 showed underexpression in pleomorphic rhabdomyosarcoma, well-differentiated liposarcoma, and synovial sarcoma. Unexpectedly, we found that a set of muscle-specific microRNAs (miRNAs; myomiRs): miR-133, miR-1, and miR-206 was significantly underexpressed in well-differentiated liposarcoma and synovial sarcoma, suggesting that they may function as tumor suppressors as described in muscle-relevant rhabdomyosarcomas. In addition, a tight linear progression of miRNA expression was identified from normal fat to dedifferentiated liposarcoma. These results suggest that miRNA expression profiles could elucidate classes of miRNAs that may elicit tumor-relevant activities in specific sarcoma subtypes.
authors.affiliation: Medical Student Research Program, The Ohio State University College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Yu
authors.affiliation: Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.|Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH, USA.|Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Mumtaz Y
authors.initials: MY
authors.lastname: Balkhi
authors.affiliation: Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.|Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Ladner
authors.affiliation: Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.|Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Hansjuerg
authors.initials: H
authors.lastname: Alder
authors.affiliation: Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Lianbo
authors.initials: L
authors.lastname: Yu
authors.affiliation: Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.affiliation: Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.|Department of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Kraybill
authors.affiliation: Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.|Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Denis C
authors.initials: DC
authors.lastname: Guttridge
authors.affiliation: Arthur G. James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.|Department of Pathology and Laboratory Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: O Hans
authors.initials: OH
authors.lastname: Iwenofu
mesh_terms: D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008080:Liposarcoma / Q000175:diagnosis / Q000235:genetics; D018208:Liposarcoma, Myxoid / Q000175:diagnosis / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000145:classification / Q000235:genetics*; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000175:diagnosis / Q000235:genetics; D012509:Sarcoma / Q000175:diagnosis / Q000235:genetics*; D013584:Sarcoma, Synovial / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
chemical_list: D035683:MicroRNAs