Cargando…
Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582145/ https://www.ncbi.nlm.nih.gov/pubmed/31213644 http://dx.doi.org/10.1038/s41598-019-45151-w |
_version_ | 1783428268257443840 |
---|---|
author | Canto, Luisa Matos do Cury, Sarah Santiloni Barros-Filho, Mateus Camargo Kupper, Bruna Elisa Catin Begnami, Maria Dirlei Ferreira de Souza Scapulatempo-Neto, Cristovam Carvalho, Robson Francisco Marchi, Fabio Albuquerque Olsen, Dorte Aalund Madsen, Jonna Skov Havelund, Birgitte Mayland Aguiar, Samuel Rogatto, Silvia Regina |
author_facet | Canto, Luisa Matos do Cury, Sarah Santiloni Barros-Filho, Mateus Camargo Kupper, Bruna Elisa Catin Begnami, Maria Dirlei Ferreira de Souza Scapulatempo-Neto, Cristovam Carvalho, Robson Francisco Marchi, Fabio Albuquerque Olsen, Dorte Aalund Madsen, Jonna Skov Havelund, Birgitte Mayland Aguiar, Samuel Rogatto, Silvia Regina |
author_sort | Canto, Luisa Matos do |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6582145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65821452019-06-26 Locally advanced rectal cancer transcriptomic-based secretome analysis reveals novel biomarkers useful to identify patients according to neoadjuvant chemoradiotherapy response Canto, Luisa Matos do Cury, Sarah Santiloni Barros-Filho, Mateus Camargo Kupper, Bruna Elisa Catin Begnami, Maria Dirlei Ferreira de Souza Scapulatempo-Neto, Cristovam Carvalho, Robson Francisco Marchi, Fabio Albuquerque Olsen, Dorte Aalund Madsen, Jonna Skov Havelund, Birgitte Mayland Aguiar, Samuel Rogatto, Silvia Regina Sci Rep Article 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. Nature Publishing Group UK 2019-06-18 /pmc/articles/PMC6582145/ /pubmed/31213644 http://dx.doi.org/10.1038/s41598-019-45151-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Canto, Luisa Matos do Cury, Sarah Santiloni Barros-Filho, Mateus Camargo Kupper, Bruna Elisa Catin Begnami, Maria Dirlei Ferreira de Souza Scapulatempo-Neto, Cristovam Carvalho, Robson Francisco Marchi, Fabio Albuquerque Olsen, Dorte Aalund Madsen, Jonna Skov Havelund, Birgitte Mayland Aguiar, Samuel Rogatto, Silvia Regina 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 |
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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582145/ https://www.ncbi.nlm.nih.gov/pubmed/31213644 http://dx.doi.org/10.1038/s41598-019-45151-w |
work_keys_str_mv | AT cantoluisamatosdo locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT curysarahsantiloni locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT barrosfilhomateuscamargo locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT kupperbrunaelisacatin locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT begnamimariadirleiferreiradesouza locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT scapulatemponetocristovam locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT carvalhorobsonfrancisco locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT marchifabioalbuquerque locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT olsendorteaalund locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT madsenjonnaskov locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT havelundbirgittemayland locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT aguiarsamuel locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse AT rogattosilviaregina locallyadvancedrectalcancertranscriptomicbasedsecretomeanalysisrevealsnovelbiomarkersusefultoidentifypatientsaccordingtoneoadjuvantchemoradiotherapyresponse |