Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/29206 http://dx.doi.org/10.1186/1471-2407-6-237 |
Resumo: | Background: Osteosarcoma is a very aggressive tumor with a propensity to metastasize and invade surrounding tissue. Identification of the molecular determinants of invasion and metastatic potential may guide the development of a rational strategy for devising specific therapies that target the pathways leading to osteosarcoma.Methods: in this study, we used pathway-focused low density expression cDNA arrays to screen for candidate genes related to tumor progression. Expression patterns of the selected genes were validated by real time PCR on osteosarcoma patient tumor samples and correlated with clinical and pathological data.Results: THBS3, SPARC and SPP1 were identified as genes differentially expressed in osteosarcoma. in particular, THBS3 was expressed at significantly high levels (p = 0.0001) in biopsies from patients with metastasis at diagnosis, which is a predictor of worse overall survival, event-free survival and relapse free survival at diagnosis. After chemotherapy, patients with tumors over-expressing THBS3 have worse relapse free survival. High SPARC expression was found in 51/55 (96.3%) osteosarcoma samples derived from 43 patients, and correlated with the worst event-free survival (p = 0.03) and relapse free survival (p = 0.07). Overexpression of SPP1 was found in 47 of 53 (89%) osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis.Conclusion: in this study three genes were identified with pattern of differential gene expression associated with a phenotypic role in metastasis and invasion. Interestingly all encode for proteins involved in extracellular remodeling suggesting potential roles in osteosarcoma progression. This is the first report on the THBS3 gene working as a stimulator of tumor progression. Higher levels of THBS3 maintain the capacity of angiogenesis. High levels of SPARC are not required for tumor progression but are necessary for tumor growth and maintenance. SPP1 is not necessary for tumor progression in osteosarcoma and may be associated with inflammatory response and bone remodeling, functioning as a good biomarker. |
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Dalla Torre, Cristiane Arruda [UNIFESP]Yoshimoto, MaisaLee, Chung-HaeJoshua, Anthony M.Toledo, Silvia Regina Caminada de [UNIFESP]Petrilli, Antonio Sergio [UNIFESP]Andrade, Joyce Anderson Duffles [UNIFESP]Chilton-MacNeill, SusanZielenska, MariaSquire, Jeremy A.Princess Margaret HospUniversidade Federal de São Paulo (UNIFESP)Hosp Sick ChildrenUniv Toronto2016-01-24T12:41:32Z2016-01-24T12:41:32Z2006-10-05Bmc Cancer. London: Biomed Central Ltd, v. 6, 10 p., 2006.1471-2407http://repositorio.unifesp.br/handle/11600/29206http://dx.doi.org/10.1186/1471-2407-6-237WOS000241285800001.pdf10.1186/1471-2407-6-237WOS:000241285800001Background: Osteosarcoma is a very aggressive tumor with a propensity to metastasize and invade surrounding tissue. Identification of the molecular determinants of invasion and metastatic potential may guide the development of a rational strategy for devising specific therapies that target the pathways leading to osteosarcoma.Methods: in this study, we used pathway-focused low density expression cDNA arrays to screen for candidate genes related to tumor progression. Expression patterns of the selected genes were validated by real time PCR on osteosarcoma patient tumor samples and correlated with clinical and pathological data.Results: THBS3, SPARC and SPP1 were identified as genes differentially expressed in osteosarcoma. in particular, THBS3 was expressed at significantly high levels (p = 0.0001) in biopsies from patients with metastasis at diagnosis, which is a predictor of worse overall survival, event-free survival and relapse free survival at diagnosis. After chemotherapy, patients with tumors over-expressing THBS3 have worse relapse free survival. High SPARC expression was found in 51/55 (96.3%) osteosarcoma samples derived from 43 patients, and correlated with the worst event-free survival (p = 0.03) and relapse free survival (p = 0.07). Overexpression of SPP1 was found in 47 of 53 (89%) osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis.Conclusion: in this study three genes were identified with pattern of differential gene expression associated with a phenotypic role in metastasis and invasion. Interestingly all encode for proteins involved in extracellular remodeling suggesting potential roles in osteosarcoma progression. This is the first report on the THBS3 gene working as a stimulator of tumor progression. Higher levels of THBS3 maintain the capacity of angiogenesis. High levels of SPARC are not required for tumor progression but are necessary for tumor growth and maintenance. SPP1 is not necessary for tumor progression in osteosarcoma and may be associated with inflammatory response and bone remodeling, functioning as a good biomarker.Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, CanadaUniversidade Federal de São Paulo, Escola Paulista Med, GRAACC, IOP,Dept Pediat, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morphol, Div Genet, BR-04023900 São Paulo, BrazilHosp Sick Children, Dept Pediat Lab Med, Toronto, ON M5G 1X8, CanadaUniv Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 2M9, CanadaUniversidade Federal de São Paulo, Escola Paulista Med, GRAACC, IOP,Dept Pediat, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morphol, Div Genet, BR-04023900 São Paulo, BrazilWeb of Science10engBiomed Central LtdBmc CancerEffects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000241285800001.pdfapplication/pdf466213${dspace.ui.url}/bitstream/11600/29206/1/WOS000241285800001.pdf5069870d6b53f73f6e5c94baf1901c52MD51open accessTEXTWOS000241285800001.pdf.txtWOS000241285800001.pdf.txtExtracted texttext/plain47887${dspace.ui.url}/bitstream/11600/29206/2/WOS000241285800001.pdf.txt0c12f4f358ce07291fa6ad68ad015c18MD52open access11600/292062023-01-30 22:17:46.656open accessoai:repositorio.unifesp.br:11600/29206Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-01-31T01:17:46Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma |
title |
Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma |
spellingShingle |
Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma Dalla Torre, Cristiane Arruda [UNIFESP] |
title_short |
Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma |
title_full |
Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma |
title_fullStr |
Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma |
title_full_unstemmed |
Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma |
title_sort |
Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma |
author |
Dalla Torre, Cristiane Arruda [UNIFESP] |
author_facet |
Dalla Torre, Cristiane Arruda [UNIFESP] Yoshimoto, Maisa Lee, Chung-Hae Joshua, Anthony M. Toledo, Silvia Regina Caminada de [UNIFESP] Petrilli, Antonio Sergio [UNIFESP] Andrade, Joyce Anderson Duffles [UNIFESP] Chilton-MacNeill, Susan Zielenska, Maria Squire, Jeremy A. |
author_role |
author |
author2 |
Yoshimoto, Maisa Lee, Chung-Hae Joshua, Anthony M. Toledo, Silvia Regina Caminada de [UNIFESP] Petrilli, Antonio Sergio [UNIFESP] Andrade, Joyce Anderson Duffles [UNIFESP] Chilton-MacNeill, Susan Zielenska, Maria Squire, Jeremy A. |
author2_role |
author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Princess Margaret Hosp Universidade Federal de São Paulo (UNIFESP) Hosp Sick Children Univ Toronto |
dc.contributor.author.fl_str_mv |
Dalla Torre, Cristiane Arruda [UNIFESP] Yoshimoto, Maisa Lee, Chung-Hae Joshua, Anthony M. Toledo, Silvia Regina Caminada de [UNIFESP] Petrilli, Antonio Sergio [UNIFESP] Andrade, Joyce Anderson Duffles [UNIFESP] Chilton-MacNeill, Susan Zielenska, Maria Squire, Jeremy A. |
description |
Background: Osteosarcoma is a very aggressive tumor with a propensity to metastasize and invade surrounding tissue. Identification of the molecular determinants of invasion and metastatic potential may guide the development of a rational strategy for devising specific therapies that target the pathways leading to osteosarcoma.Methods: in this study, we used pathway-focused low density expression cDNA arrays to screen for candidate genes related to tumor progression. Expression patterns of the selected genes were validated by real time PCR on osteosarcoma patient tumor samples and correlated with clinical and pathological data.Results: THBS3, SPARC and SPP1 were identified as genes differentially expressed in osteosarcoma. in particular, THBS3 was expressed at significantly high levels (p = 0.0001) in biopsies from patients with metastasis at diagnosis, which is a predictor of worse overall survival, event-free survival and relapse free survival at diagnosis. After chemotherapy, patients with tumors over-expressing THBS3 have worse relapse free survival. High SPARC expression was found in 51/55 (96.3%) osteosarcoma samples derived from 43 patients, and correlated with the worst event-free survival (p = 0.03) and relapse free survival (p = 0.07). Overexpression of SPP1 was found in 47 of 53 (89%) osteosarcomas correlating with better overall survival, event-free survival and relapse free survival at diagnosis.Conclusion: in this study three genes were identified with pattern of differential gene expression associated with a phenotypic role in metastasis and invasion. Interestingly all encode for proteins involved in extracellular remodeling suggesting potential roles in osteosarcoma progression. This is the first report on the THBS3 gene working as a stimulator of tumor progression. Higher levels of THBS3 maintain the capacity of angiogenesis. High levels of SPARC are not required for tumor progression but are necessary for tumor growth and maintenance. SPP1 is not necessary for tumor progression in osteosarcoma and may be associated with inflammatory response and bone remodeling, functioning as a good biomarker. |
publishDate |
2006 |
dc.date.issued.fl_str_mv |
2006-10-05 |
dc.date.accessioned.fl_str_mv |
2016-01-24T12:41:32Z |
dc.date.available.fl_str_mv |
2016-01-24T12:41:32Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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dc.identifier.citation.fl_str_mv |
Bmc Cancer. London: Biomed Central Ltd, v. 6, 10 p., 2006. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/29206 http://dx.doi.org/10.1186/1471-2407-6-237 |
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1471-2407 |
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WOS000241285800001.pdf |
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10.1186/1471-2407-6-237 |
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WOS:000241285800001 |
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Bmc Cancer. London: Biomed Central Ltd, v. 6, 10 p., 2006. 1471-2407 WOS000241285800001.pdf 10.1186/1471-2407-6-237 WOS:000241285800001 |
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http://repositorio.unifesp.br/handle/11600/29206 http://dx.doi.org/10.1186/1471-2407-6-237 |
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Biomed Central Ltd |
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