Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

<p>Abstract</p> <p>Background</p> <p>Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS) accounts for ap...

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Main Authors: Rao Nagesha AS, van Wolferen Monique E, Kirpensteijn Jolle, Selvarajah Gayathri T, Fieten Hille, Mol Jan A
Format: Article
Language:English
Published: BMC 2009-09-01
Series:Molecular Cancer
Online Access:http://www.molecular-cancer.com/content/8/1/72
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author Rao Nagesha AS
van Wolferen Monique E
Kirpensteijn Jolle
Selvarajah Gayathri T
Fieten Hille
Mol Jan A
author_facet Rao Nagesha AS
van Wolferen Monique E
Kirpensteijn Jolle
Selvarajah Gayathri T
Fieten Hille
Mol Jan A
author_sort Rao Nagesha AS
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS.</p> <p>Results</p> <p>The 32 tumors were classified into two prognostic groups based on survival time (ST). They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months) and long survivors (dogs with better prognosis: surviving 6 months or longer). Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans.</p> <p>Conclusion</p> <p>A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the dog a suitable pre-clinical model for future 'novel' therapeutic approaches where the current research has provided new insights on prognostic genes, molecular pathways and mechanisms involved in OS pathogenesis and disease progression.</p>
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spelling doaj.art-9225d5826608439394335266728d1d862022-12-21T23:32:06ZengBMCMolecular Cancer1476-45982009-09-01817210.1186/1476-4598-8-72Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival timesRao Nagesha ASvan Wolferen Monique EKirpensteijn JolleSelvarajah Gayathri TFieten HilleMol Jan A<p>Abstract</p> <p>Background</p> <p>Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS.</p> <p>Results</p> <p>The 32 tumors were classified into two prognostic groups based on survival time (ST). They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months) and long survivors (dogs with better prognosis: surviving 6 months or longer). Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans.</p> <p>Conclusion</p> <p>A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the dog a suitable pre-clinical model for future 'novel' therapeutic approaches where the current research has provided new insights on prognostic genes, molecular pathways and mechanisms involved in OS pathogenesis and disease progression.</p>http://www.molecular-cancer.com/content/8/1/72
spellingShingle Rao Nagesha AS
van Wolferen Monique E
Kirpensteijn Jolle
Selvarajah Gayathri T
Fieten Hille
Mol Jan A
Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times
Molecular Cancer
title Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times
title_full Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times
title_fullStr Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times
title_full_unstemmed Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times
title_short Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times
title_sort gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times
url http://www.molecular-cancer.com/content/8/1/72
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AT selvarajahgayathrit geneexpressionprofilingofcanineosteosarcomarevealsgenesassociatedwithshortandlongsurvivaltimes
AT fietenhille geneexpressionprofilingofcanineosteosarcomarevealsgenesassociatedwithshortandlongsurvivaltimes
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