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Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer

Breast cancer stromal compartment, may influence responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy (neoCT) in locally advanced breast cancer (LABC). The tumor s...

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Autores principales: Katayama, Maria Lucia Hirata, Vieira, René Aloísio da Costa, Andrade, Victor Piana, Roela, Rosimeire Aparecida, Lima, Luiz Guilherme Cernaglia Aureliano, Kerr, Ligia Maria, de Campos, Adriano Polpo, Pereira, Carlos Alberto de Bragança, Serio, Pedro Adolpho de Menezes Pacheco, Encinas, Giselly, Maistro, Simone, Petroni, Matheus de Almeida Leite, Brentani, Maria Mitzi, Folgueira, Maria Aparecida Azevedo Koike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953077/
https://www.ncbi.nlm.nih.gov/pubmed/31817155
http://dx.doi.org/10.3390/cells8121566
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author Katayama, Maria Lucia Hirata
Vieira, René Aloísio da Costa
Andrade, Victor Piana
Roela, Rosimeire Aparecida
Lima, Luiz Guilherme Cernaglia Aureliano
Kerr, Ligia Maria
de Campos, Adriano Polpo
Pereira, Carlos Alberto de Bragança
Serio, Pedro Adolpho de Menezes Pacheco
Encinas, Giselly
Maistro, Simone
Petroni, Matheus de Almeida Leite
Brentani, Maria Mitzi
Folgueira, Maria Aparecida Azevedo Koike
author_facet Katayama, Maria Lucia Hirata
Vieira, René Aloísio da Costa
Andrade, Victor Piana
Roela, Rosimeire Aparecida
Lima, Luiz Guilherme Cernaglia Aureliano
Kerr, Ligia Maria
de Campos, Adriano Polpo
Pereira, Carlos Alberto de Bragança
Serio, Pedro Adolpho de Menezes Pacheco
Encinas, Giselly
Maistro, Simone
Petroni, Matheus de Almeida Leite
Brentani, Maria Mitzi
Folgueira, Maria Aparecida Azevedo Koike
author_sort Katayama, Maria Lucia Hirata
collection PubMed
description Breast cancer stromal compartment, may influence responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy (neoCT) in locally advanced breast cancer (LABC). The tumor samples were collected from 44 patients with LABC (29 estrogen receptor (ER) positive and 15 ER negative) before the start of any treatment. Neoadjuvant chemotherapy consisted of doxorubicin and cyclophosphamide, followed by paclitaxel. Response was defined as downstaging to maximum ypT1a-b/ypN0. The stromal cells, mainly composed of fibroblast and immune cells, were microdissected from fresh frozen tumor samples and gene expression profile was determined using Agilent SurePrint G3 Human Gene Expression microarrays. Expression levels were compared using MeV (MultiExperiment Viewer) software, applying SAM (significance analysis of microarrays). To classify samples according to tumor response, the order of median based on confidence statements (MedOr) was used, and to identify gene sets correlated with the phenotype downstaging, gene set enrichment analysis (GSEA). Nine patients presented disease downstaging. Eleven sequences (FDR 17) were differentially expressed, all of which (except H2AFJ) more expressed in responsive tumors, including PTCHD1 and genes involved in abnormal cytotoxic T cell physiology, TOX, LY75, and SH2D1A. The following four pairs of markers could correctly classify all tumor samples according to response: PTCHD1/PDXDC2P, LOC100506731/NEURL4, SH2D1A/ENST00000478672, and TOX/H2AFJ. Gene sets correlated with tumor downstaging (FDR < 0.01) were mainly involved in immune response or lymphocyte activation, including CD47, LCK, NCK1, CD24, CD3E, ZAP70, FOXP3, and CD74, among others. In locally advanced breast cancer, stromal cells may present specific features of immune response that may be associated with chemotherapy response.
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spelling pubmed-69530772020-01-23 Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Katayama, Maria Lucia Hirata Vieira, René Aloísio da Costa Andrade, Victor Piana Roela, Rosimeire Aparecida Lima, Luiz Guilherme Cernaglia Aureliano Kerr, Ligia Maria de Campos, Adriano Polpo Pereira, Carlos Alberto de Bragança Serio, Pedro Adolpho de Menezes Pacheco Encinas, Giselly Maistro, Simone Petroni, Matheus de Almeida Leite Brentani, Maria Mitzi Folgueira, Maria Aparecida Azevedo Koike Cells Article Breast cancer stromal compartment, may influence responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy (neoCT) in locally advanced breast cancer (LABC). The tumor samples were collected from 44 patients with LABC (29 estrogen receptor (ER) positive and 15 ER negative) before the start of any treatment. Neoadjuvant chemotherapy consisted of doxorubicin and cyclophosphamide, followed by paclitaxel. Response was defined as downstaging to maximum ypT1a-b/ypN0. The stromal cells, mainly composed of fibroblast and immune cells, were microdissected from fresh frozen tumor samples and gene expression profile was determined using Agilent SurePrint G3 Human Gene Expression microarrays. Expression levels were compared using MeV (MultiExperiment Viewer) software, applying SAM (significance analysis of microarrays). To classify samples according to tumor response, the order of median based on confidence statements (MedOr) was used, and to identify gene sets correlated with the phenotype downstaging, gene set enrichment analysis (GSEA). Nine patients presented disease downstaging. Eleven sequences (FDR 17) were differentially expressed, all of which (except H2AFJ) more expressed in responsive tumors, including PTCHD1 and genes involved in abnormal cytotoxic T cell physiology, TOX, LY75, and SH2D1A. The following four pairs of markers could correctly classify all tumor samples according to response: PTCHD1/PDXDC2P, LOC100506731/NEURL4, SH2D1A/ENST00000478672, and TOX/H2AFJ. Gene sets correlated with tumor downstaging (FDR < 0.01) were mainly involved in immune response or lymphocyte activation, including CD47, LCK, NCK1, CD24, CD3E, ZAP70, FOXP3, and CD74, among others. In locally advanced breast cancer, stromal cells may present specific features of immune response that may be associated with chemotherapy response. MDPI 2019-12-04 /pmc/articles/PMC6953077/ /pubmed/31817155 http://dx.doi.org/10.3390/cells8121566 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Katayama, Maria Lucia Hirata
Vieira, René Aloísio da Costa
Andrade, Victor Piana
Roela, Rosimeire Aparecida
Lima, Luiz Guilherme Cernaglia Aureliano
Kerr, Ligia Maria
de Campos, Adriano Polpo
Pereira, Carlos Alberto de Bragança
Serio, Pedro Adolpho de Menezes Pacheco
Encinas, Giselly
Maistro, Simone
Petroni, Matheus de Almeida Leite
Brentani, Maria Mitzi
Folgueira, Maria Aparecida Azevedo Koike
Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
title Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
title_full Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
title_fullStr Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
title_full_unstemmed Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
title_short Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer
title_sort stromal cell signature associated with response to neoadjuvant chemotherapy in locally advanced breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953077/
https://www.ncbi.nlm.nih.gov/pubmed/31817155
http://dx.doi.org/10.3390/cells8121566
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