Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , |
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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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) |
repository.mail.fl_str_mv |
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1808128621839122432 |