title: Gene expression profiling of giant cell tumor of bone reveals downregulation of extracellular matrix components decorin and lumican associated with lung metastasis.
abstract: Giant cell tumor of bone (GCTB) displays worrisome clinical features such as local recurrence and occasionally metastatic disease which are unpredictable by morphology. Additional routinely usable biomarkers do not exist. Gene expression profiles of six clinically defined groups of GCTB and one group of aneurysmal bone cyst (ABC) were determined by microarray (n = 33). The most promising differentially expressed genes were validated by Q-PCR as potential biomarkers in a larger patient group (n = 41). Corresponding protein expression was confirmed by immunohistochemistry. Unsupervised hierarchical clustering reveals a metastatic GCTB cluster, a heterogeneous, non-metastatic GCTB cluster, and a primary ABC cluster. Balanced score testing indicates that lumican (LUM) and decorin (DCN) are the most promising biomarkers as they have lower level of expression in the metastatic group. Expression of dermatopontin (DPT) was significantly lower in recurrent tumors. Validation of the results was performed by paired and unpaired t test in primary GCTB and corresponding metastases, which proved that the differential expression of LUM and DCN is tumor specific rather than location specific. Our findings show that several genes related to extracellular matrix integrity (LUM, DCN, and DPT) are differentially expressed and may serve as biomarkers for metastatic and recurrent GCTB.
authors.affiliation: N. Goormaghtigh Institute of Pathology, Ghent, Belgium, marusyalieveld@hotmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Lieveld
authors.forename: E
authors.initials: E
authors.lastname: Bodson
authors.forename: G
authors.initials: G
authors.lastname: De Boeck
authors.forename: B
authors.initials: B
authors.lastname: Nouman
authors.forename: A M
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: E
authors.initials: E
authors.lastname: Korsching
authors.forename: M S
authors.initials: MS
authors.lastname: Benassi
authors.forename: P
authors.initials: P
authors.lastname: Picci
authors.forename: G
authors.initials: G
authors.lastname: Sys
authors.forename: B
authors.initials: B
authors.lastname: Poffyn
authors.forename: N A
authors.initials: NA
authors.lastname: Athanasou
authors.forename: P C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: R G
authors.initials: RG
authors.lastname: Forsyth
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D016000:Cluster Analysis; D058575:Decorin / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018212:Giant Cell Tumor of Bone / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007632:Keratan Sulfate / Q000096:biosynthesis / Q000235:genetics; D000071234:Lumican; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; C082019:DPT protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604306:LUM protein, human; D000071234:Lumican; D007632:Keratan Sulfate