Microarray analysis identifies distinct gene expression profiles associated with histological subtype in human osteosarcoma

Kubista, Bernd; Klinglmueller, Florian; Bilban, Martin; Pfeiffer, Martin; Lass, Richard; Giurea, Alexander; Funovics, Phillipp T.; Toma, Cyril D.; Dominkus, Martin; Kotz, R.; Thalhammer, Theresia; Trieb, Klemens; Zettl, Teresa; Singer, Christian F.

doi:10.1007/s00264-010-0996-6

Cited by 37 publications

(35 citation statements)

References 36 publications

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“…Earlier studies have similarly found clear downregulation of Wnt signalling in 25 high-grade prechemotherapy biopsies [36]. In many studies the comparisons are not made between healthy bone and osteosarcoma, therefore not all published gene expression-profiling studies are comparable with ours [37,38]. Therefore, some controversies exist about the involvement of Wnt signalling pathway in OS development.…”

Section: Discussionmentioning

confidence: 90%

Transcriptome analysis of osteosarcoma identifies suppression of wnt pathway and up-regulation of adiponectin as potential biomarker

Märtson¹,

Kõks²,

Reimann³

et al. 2013

Genomics Discov

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Osteosarcoma (OS) is primary malignant bone tumour with complicated early diagnosis. There are no specific markers currently available for predicting the prognosis and chemosensitivity of OS. In present study we performed transcriptome profiling of single patient tumour tissue with RNA-seq technology. We analysed surgically removed sarcoma sample from single 16 years old male patient. Transciptome analysis was done with RNA-seq technology, bioinformatics with Lifescope and R Bioconductor. Validation experiments were done with quantitative real-time PCR (QRTPCR). After quality and coverage filtering, RNA-seq experiment resulted 29,311,899 mapped reads for sarcoma and 22,099,159 mapped reads for normal bone tissue. 65 genes were differentially expressed with FDR corrected statistical significance below 0.05. Seven genes were down-regulated and 58 genes were up-regulated in sarcoma. The most highly up-regulated gene in sarcoma was adiponectin, ADIPOQ (with adjusted p-value 5.5E-07, log2 fold change was 7.9). Many of the genes we found are related to the adipose tissue metabolism (ADIPOQ, PLIN1, FABP4) and to the Wnt signalling suppression (WIF1, SOST). We also found novel fusion transcript between the genes LMTK2 and ZSWIM5. LMTK2 is lemur tyrosine kinase 2, and it has been shown to be involved in NGF-TrkA signalling. Interestingly, studies support the involvement of LMTK2 in development of prostate cancer. ZSWIM5 is zinc finger SWIM domain protein 5 and its function is not known. Immunohistochemical analysis confirmed positive staining for adiponectin in osteosarcoma. This paper is a good illustration how transcriptome analysis can find new biomarkers and targets for complex diseases.

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Section: Discussionmentioning

confidence: 90%

Transcriptome analysis of osteosarcoma identifies suppression of wnt pathway and up-regulation of adiponectin as potential biomarker

Märtson¹,

Kõks²,

Reimann³

et al. 2013

Genomics Discov

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“…Decorin had severalfold reduced expression in osteoblastic osteosarcoma patients compared with non-osteoblastic osteosarcoma patients, which could be correlated to a poorer prognosis of the first patient group (80). Immunohistochemistry using polyclonal and monoclonal antibodies against ECM molecules, including decorin, has proved to be a useful tool for the differential characterization of osteoid in a series of 20 osteosarcomas with different variants of osteoid formation (81).…”

Section: Roles In Bone Tumor Progressionmentioning

confidence: 99%

The Biology of Small Leucine-rich Proteoglycans in Bone Pathophysiology

Nikitovic

Aggelidakis

Young

et al. 2012

Journal of Biological Chemistry

134

127

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The class of small leucine-rich proteoglycans (SLRPs) is a family of homologous proteoglycans harboring relatively small (36 -42 kDa) protein cores compared with the larger cartilage and mesenchymal proteoglycans. SLRPs have been localized to most skeletal regions, with specific roles designated during all phases of bone formation, including periods relating to cell proliferation, organic matrix deposition, remodeling, and mineral deposition. This is mediated by key signaling pathways regulating the osteogenic program, including the activities of TGF-␤, bone morphogenetic protein, Wnt, and NF-B, which influence both the number of available osteogenic precursors and their subsequent development, differentiation, and function. On the other hand, SLRP depletion is correlated with degenerative diseases such as osteoporosis and ectopic bone formation. This minireview will focus on the SLRP roles in bone physiology and pathology.

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“…In particular, they found significantly modulated the expression of several genes involved in the formation of extracellular matrix, including fibulin-1, already known to be involved in cell morphology modulation, growth and invasion of sarcoma cells (Qing et al, 1997) and suggest that fibulin-1 could be exploited as potential therapeutic target in the future (Kubista et al, 2011).…”

Section: ) Mesenchymal Cancers Osteosarcomamentioning

confidence: 99%