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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6953077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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