Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response

Detalhes bibliográficos
Autor(a) principal: Canto, Luisa Matos do
Data de Publicação: 2019
Outros Autores: Cury, Sarah Santiloni [UNESP], Barros-Filho, Mateus Camargo, Kupper, Bruna Elisa Catin, Begnami, Maria Dirlei Ferreira de Souza, Scapulatempo-Neto, Cristovam, Carvalho, Robson Francisco [UNESP], Marchi, Fabio Albuquerque, Olsen, Dorte Aalund, Madsen, Jonna Skov, Havelund, Birgitte Mayland, Aguiar, Samuel, Rogatto, Silvia Regina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1038/s41598-019-45151-w
http://hdl.handle.net/11449/190424
Resumo: Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.
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spelling Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy responseMost patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)International Research Center - CIPE A.C.Camargo Cancer CenterDepartment of Clinical Genetics University Hospital of Southern DenmarkDepartment of Morphology – Institute of Bioscience São Paulo State University (UNESP)Department of Pelvic Surgery A.C.Camargo Cancer CenterDepartment of Pathology A.C.Camargo Cancer CenterMolecular Oncology Research Center Barretos and Diagnósticos da América (DASA)Department of Biochemistry and Immunology University Hospital of Southern DenmarkDanish Colorectal Cancer Center SouthInstitute of Regional Health Research Faculty of Health Sciences University of Southern DenmarkDepartment of Oncology University Hospital of Southern DenmarkDepartment of Morphology – Institute of Bioscience São Paulo State University (UNESP)FAPESP: 2008/57887-9FAPESP: 2014/06323-9FAPESP: 2015/25803-4CNPq: 573589/08-9A.C.Camargo Cancer CenterUniversity Hospital of Southern DenmarkUniversidade Estadual Paulista (Unesp)and Diagnósticos da América (DASA)Danish Colorectal Cancer Center SouthUniversity of Southern DenmarkCanto, Luisa Matos doCury, Sarah Santiloni [UNESP]Barros-Filho, Mateus CamargoKupper, Bruna Elisa CatinBegnami, Maria Dirlei Ferreira de SouzaScapulatempo-Neto, CristovamCarvalho, Robson Francisco [UNESP]Marchi, Fabio AlbuquerqueOlsen, Dorte AalundMadsen, Jonna SkovHavelund, Birgitte MaylandAguiar, SamuelRogatto, Silvia Regina2019-10-06T17:12:46Z2019-10-06T17:12:46Z2019-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-019-45151-wScientific Reports, v. 9, n. 1, 2019.2045-2322http://hdl.handle.net/11449/19042410.1038/s41598-019-45151-w2-s2.0-85067623037Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScientific Reportsinfo:eu-repo/semantics/openAccess2021-10-22T21:09:46Zoai:repositorio.unesp.br:11449/190424Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:13:42.418650Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
title Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
spellingShingle Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
Canto, Luisa Matos do
title_short Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
title_full Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
title_fullStr Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
title_full_unstemmed Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
title_sort Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
author Canto, Luisa Matos do
author_facet Canto, Luisa Matos do
Cury, Sarah Santiloni [UNESP]
Barros-Filho, Mateus Camargo
Kupper, Bruna Elisa Catin
Begnami, Maria Dirlei Ferreira de Souza
Scapulatempo-Neto, Cristovam
Carvalho, Robson Francisco [UNESP]
Marchi, Fabio Albuquerque
Olsen, Dorte Aalund
Madsen, Jonna Skov
Havelund, Birgitte Mayland
Aguiar, Samuel
Rogatto, Silvia Regina
author_role author
author2 Cury, Sarah Santiloni [UNESP]
Barros-Filho, Mateus Camargo
Kupper, Bruna Elisa Catin
Begnami, Maria Dirlei Ferreira de Souza
Scapulatempo-Neto, Cristovam
Carvalho, Robson Francisco [UNESP]
Marchi, Fabio Albuquerque
Olsen, Dorte Aalund
Madsen, Jonna Skov
Havelund, Birgitte Mayland
Aguiar, Samuel
Rogatto, Silvia Regina
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv A.C.Camargo Cancer Center
University Hospital of Southern Denmark
Universidade Estadual Paulista (Unesp)
and Diagnósticos da América (DASA)
Danish Colorectal Cancer Center South
University of Southern Denmark
dc.contributor.author.fl_str_mv Canto, Luisa Matos do
Cury, Sarah Santiloni [UNESP]
Barros-Filho, Mateus Camargo
Kupper, Bruna Elisa Catin
Begnami, Maria Dirlei Ferreira de Souza
Scapulatempo-Neto, Cristovam
Carvalho, Robson Francisco [UNESP]
Marchi, Fabio Albuquerque
Olsen, Dorte Aalund
Madsen, Jonna Skov
Havelund, Birgitte Mayland
Aguiar, Samuel
Rogatto, Silvia Regina
description Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. We performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between complete (pCR) and incomplete responders to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome, and Plasma Proteome). Seventeen potentially secreted candidates (pCR = 1, pIR = 13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC and association with nCRT response (GSE68204). The expression of circulating amphiregulin and cMET proteins was confirmed in serum from 14 LARC patients. Future studies in liquid biopsies could confirm the utility of these proteins for personalized treatment in LARC patients.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-06T17:12:46Z
2019-10-06T17:12:46Z
2019-12-01
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/10.1038/s41598-019-45151-w
Scientific Reports, v. 9, n. 1, 2019.
2045-2322
http://hdl.handle.net/11449/190424
10.1038/s41598-019-45151-w
2-s2.0-85067623037
url http://dx.doi.org/10.1038/s41598-019-45151-w
http://hdl.handle.net/11449/190424
identifier_str_mv Scientific Reports, v. 9, n. 1, 2019.
2045-2322
10.1038/s41598-019-45151-w
2-s2.0-85067623037
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Scientific Reports
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
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)
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