Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0102281 http://hdl.handle.net/11449/117390 |
Resumo: | Background: Undifferentiated Pleomorphic Sarcoma (UPS) and high-grade Leiomyosarcoma (LMS) are soft tissue tumors with an aggressive clinical behavior, frequently developing local recurrence and distant metastases. Despite several gene expression studies involving soft tissue sarcomas, the potential to identify molecular markers has been limited, mostly due to small sample size, in-group heterogeneity and absence of detailed clinical data.Materials and Methods: Gene expression profiling was performed for 22 LMS and 22 UPS obtained from untreated patients. To assess the relevance of the gene signature, a meta-analysis was performed using five published studies. Four genes (BAD, MYOCD, SRF and SRC) selected from the gene signature, meta-analysis and functional in silico analysis were further validated by quantitative PCR. In addition, protein-protein interaction analysis was applied to validate the data. SRC protein immunolabeling was assessed in 38 UPS and 52 LMS.Results: We identified 587 differentially expressed genes between LMS and UPS, of which 193 corroborated with other studies. Cluster analysis of the data failed to discriminate LMS from UPS, although it did reveal a distinct molecular profile for retroperitoneal LMS, which was characterized by the over-expression of smooth muscle-specific genes. Significantly higher levels of expression for BAD, SRC, SRF, and MYOCD were confirmed in LMS when compared with UPS. SRC was the most value discriminator to distinguish both sarcomas and presented the highest number of interaction in the in silico protein-protein analysis. SRC protein labeling showed high specificity and a positive predictive value therefore making it a candidate for use as a diagnostic marker in LMS.Conclusions: Retroperitoneal LMS presented a unique gene signature. SRC is a putative diagnostic marker to differentiate LMS from UPS. |
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Repositório Institucional da UNESP |
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spelling |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic markerBackground: Undifferentiated Pleomorphic Sarcoma (UPS) and high-grade Leiomyosarcoma (LMS) are soft tissue tumors with an aggressive clinical behavior, frequently developing local recurrence and distant metastases. Despite several gene expression studies involving soft tissue sarcomas, the potential to identify molecular markers has been limited, mostly due to small sample size, in-group heterogeneity and absence of detailed clinical data.Materials and Methods: Gene expression profiling was performed for 22 LMS and 22 UPS obtained from untreated patients. To assess the relevance of the gene signature, a meta-analysis was performed using five published studies. Four genes (BAD, MYOCD, SRF and SRC) selected from the gene signature, meta-analysis and functional in silico analysis were further validated by quantitative PCR. In addition, protein-protein interaction analysis was applied to validate the data. SRC protein immunolabeling was assessed in 38 UPS and 52 LMS.Results: We identified 587 differentially expressed genes between LMS and UPS, of which 193 corroborated with other studies. Cluster analysis of the data failed to discriminate LMS from UPS, although it did reveal a distinct molecular profile for retroperitoneal LMS, which was characterized by the over-expression of smooth muscle-specific genes. Significantly higher levels of expression for BAD, SRC, SRF, and MYOCD were confirmed in LMS when compared with UPS. SRC was the most value discriminator to distinguish both sarcomas and presented the highest number of interaction in the in silico protein-protein analysis. SRC protein labeling showed high specificity and a positive predictive value therefore making it a candidate for use as a diagnostic marker in LMS.Conclusions: Retroperitoneal LMS presented a unique gene signature. SRC is a putative diagnostic marker to differentiate LMS from UPS.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)AC Camargo Canc Ctr, Res Ctr CIPE, Neogene Lab, Sao Paulo, BrazilUniv Sao Paulo, Interinst Grad Program Bioinformat, Math & Stat Inst, Sao Paulo, BrazilUNESP Sao Paulo State Univ, Sch Med, Dept Pathol, Sao Paulo, BrazilBarretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Pelv Surg, Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Pathol, Sao Paulo, BrazilUNESP Sao Paulo State Univ, Sch Med, Dept Urol, Sao Paulo, BrazilUNESP Sao Paulo State Univ, Sch Med, Dept Pathol, Sao Paulo, BrazilUNESP Sao Paulo State Univ, Sch Med, Dept Urol, Sao Paulo, BrazilPublic Library ScienceAC Camargo Canc CtrUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Barretos Canc HospVillacis, Rolando A. R.Silveira, Sara M.Barros-Filho, Mateus C.Marchi, Fabio A.Domingues, Maria Aparecida Custódio [UNESP]Scapulatempo-Neto, CristovamAguiar, SamuelLopes, AdemarCunha, Isabela W.Rogatto, Silvia Regina [UNESP]2015-03-18T15:56:01Z2015-03-18T15:56:01Z2014-07-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttp://dx.doi.org/10.1371/journal.pone.0102281Plos One. San Francisco: Public Library Science, v. 9, n. 7, 8 p., 2014.1932-6203http://hdl.handle.net/11449/11739010.1371/journal.pone.0102281WOS:000341306600056WOS000341306600056.pdf0585723113037140Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPlos One2.7661,164info:eu-repo/semantics/openAccess2023-10-05T06:06:48Zoai:repositorio.unesp.br:11449/117390Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:05:36.139719Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker |
title |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker |
spellingShingle |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker Villacis, Rolando A. R. |
title_short |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker |
title_full |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker |
title_fullStr |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker |
title_full_unstemmed |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker |
title_sort |
Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker |
author |
Villacis, Rolando A. R. |
author_facet |
Villacis, Rolando A. R. Silveira, Sara M. Barros-Filho, Mateus C. Marchi, Fabio A. Domingues, Maria Aparecida Custódio [UNESP] Scapulatempo-Neto, Cristovam Aguiar, Samuel Lopes, Ademar Cunha, Isabela W. Rogatto, Silvia Regina [UNESP] |
author_role |
author |
author2 |
Silveira, Sara M. Barros-Filho, Mateus C. Marchi, Fabio A. Domingues, Maria Aparecida Custódio [UNESP] Scapulatempo-Neto, Cristovam Aguiar, Samuel Lopes, Ademar Cunha, Isabela W. Rogatto, Silvia Regina [UNESP] |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
AC Camargo Canc Ctr Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) Barretos Canc Hosp |
dc.contributor.author.fl_str_mv |
Villacis, Rolando A. R. Silveira, Sara M. Barros-Filho, Mateus C. Marchi, Fabio A. Domingues, Maria Aparecida Custódio [UNESP] Scapulatempo-Neto, Cristovam Aguiar, Samuel Lopes, Ademar Cunha, Isabela W. Rogatto, Silvia Regina [UNESP] |
description |
Background: Undifferentiated Pleomorphic Sarcoma (UPS) and high-grade Leiomyosarcoma (LMS) are soft tissue tumors with an aggressive clinical behavior, frequently developing local recurrence and distant metastases. Despite several gene expression studies involving soft tissue sarcomas, the potential to identify molecular markers has been limited, mostly due to small sample size, in-group heterogeneity and absence of detailed clinical data.Materials and Methods: Gene expression profiling was performed for 22 LMS and 22 UPS obtained from untreated patients. To assess the relevance of the gene signature, a meta-analysis was performed using five published studies. Four genes (BAD, MYOCD, SRF and SRC) selected from the gene signature, meta-analysis and functional in silico analysis were further validated by quantitative PCR. In addition, protein-protein interaction analysis was applied to validate the data. SRC protein immunolabeling was assessed in 38 UPS and 52 LMS.Results: We identified 587 differentially expressed genes between LMS and UPS, of which 193 corroborated with other studies. Cluster analysis of the data failed to discriminate LMS from UPS, although it did reveal a distinct molecular profile for retroperitoneal LMS, which was characterized by the over-expression of smooth muscle-specific genes. Significantly higher levels of expression for BAD, SRC, SRF, and MYOCD were confirmed in LMS when compared with UPS. SRC was the most value discriminator to distinguish both sarcomas and presented the highest number of interaction in the in silico protein-protein analysis. SRC protein labeling showed high specificity and a positive predictive value therefore making it a candidate for use as a diagnostic marker in LMS.Conclusions: Retroperitoneal LMS presented a unique gene signature. SRC is a putative diagnostic marker to differentiate LMS from UPS. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-07-16 2015-03-18T15:56:01Z 2015-03-18T15:56:01Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1371/journal.pone.0102281 Plos One. San Francisco: Public Library Science, v. 9, n. 7, 8 p., 2014. 1932-6203 http://hdl.handle.net/11449/117390 10.1371/journal.pone.0102281 WOS:000341306600056 WOS000341306600056.pdf 0585723113037140 |
url |
http://dx.doi.org/10.1371/journal.pone.0102281 http://hdl.handle.net/11449/117390 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 9, n. 7, 8 p., 2014. 1932-6203 10.1371/journal.pone.0102281 WOS:000341306600056 WOS000341306600056.pdf 0585723113037140 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Plos One 2.766 1,164 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
8 application/pdf |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808128314289684480 |