Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker

Detalhes bibliográficos
Autor(a) principal: Villacis, Rolando A. R.
Data de Publicação: 2014
Outros Autores: 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]
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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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
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dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
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