title: MicroRNA expression profiles in metastatic and non-metastatic giant cell tumor of bone.
abstract: Giant cell tumor of bone (GCTB) is a skeletal neoplasm, a locally aggressive tumor that occasionally metastasizes to the lungs. To identify novel biomarkers associated with GCTB progression and metastasis, we performed a miRNA microarray on ten primary tumors of GCTB, of which five developed lung metastases and the rest remained metastasis-free. Between metastatic and non-metastatic GCTB, 12 miRNAs were differentially expressed (such as miR-136, miR-513a-5p, miR-494, miR-224, and miR-542-5p). A decreased level of miR-136 in metastatic versus non-metastatic GCTB was significantly confirmed by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) (p=0.04). To identify potential target genes for the differentially expressed miRNAs, we used three target prediction databases. Then, to functionally validate the potential target genes of the differentially expressed miRNAs, we re-analyzed our previous gene expression data from the same ten patients. Eight genes such as NFIB, TNC, and FLRT2 were inversely expressed relative to their predicted miRNA regulators. NFIB expression correlated in metastatic GCTB with no or low expression of miR-136, and this gene was selected for further verification with qRT-PCR and immunohistochemistry. Verification of NFIB mRNA and protein by qRT-PCR showed elevated expression levels in metastatic GCTBs. Further, the protein expression level of NFIB was tested in an independent validation cohort of 74 primary archival GCTB specimens. In the primary tumors that developed metastases compared to the disease-free group, NFIB protein was moderately to strongly expressed at a higher frequency. Thus, in GCTB, miR-136 and NFIB may serve as prognostic makers.
authors.affiliation: Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Neda
authors.initials: N
authors.lastname: Mosakhani
authors.forename: Laura
authors.initials: L
authors.lastname: Pazzaglia
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Benassi
authors.forename: Ioana
authors.initials: I
authors.lastname: Borze
authors.forename: Irene
authors.initials: I
authors.lastname: Quattrini
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D018212:Giant Cell Tumor of Bone / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000556:secondary; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051839:NFI Transcription Factors / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; C577037:MIRN136 microRNA, human; D035683:MicroRNAs; D051839:NFI Transcription Factors; C110754:NFIB protein, human