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

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Hirata Katayama, Maria Lucia ^[1] ; Costa Vieira, Rene Aloisio ^[2] ; Andrade, Victor Piana ^[3] ; Roela, Rosimeire Aparecida ^[1] ; Cernaglia Aureliano Lima, Luiz Guilherme ^[3] ; Kerr, Ligia Maria ^[4] ; de Campos, Adriano Polpo ^{[5, 6]} ; de Braganca Pereira, Carlos Alberto ^[7] ; de Menezes Pacheco Serio, Pedro Adolpho ^[1] ; Encinas, Giselly ^[1] ; Maistro, Simone ^[1] ; Leite Petroni, Matheus de Almeida ^[1] ; Brentani, Maria Mitzi ^[1] ; Azevedo Koike Folgueira, Maria Aparecida ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Dept Radiol & Oncol, Ctr Invest Translac Oncol, Inst Canc Estado Sao Pa, BR-01246000 Sao Paulo, SP - Brazil

^[2] Hosp Canc Barretos, Dept Mastol, BR-14784400 Barretos, SP - Brazil

^[3] AC Camargo Canc Ctr, BR-01525001 Sao Paulo, SP - Brazil

^[4] Hosp Canc Barretos, Dept Patol, BR-14784400 Barretos, SP - Brazil

^[5] Univ Fed Sao Carlos, Ctr Ciencias Exatas & Tecnol, Dept Estat, BR-13565905 Sao Carlos, SP - Brazil

^[6] Univ Western Australia, Dept Math & Stat, M019, 35 Stirling Highway, Crawley, WA 6009 - Australia

^[7] Univ Sao Paulo, Inst Matemat & Estat, Dept Estat, BR-05508090 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELLS; v. 8, n. 12 DEC 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 09/10088-7 - Expressão gênica de fibroblastos associados a carcinomas de mama classificados em subtipos de acordo com receptores de estrógeno e progesterona e C-ERBB2
• Beneficiário: Maria Mitzi Brentani
• Modalidade de apoio: Auxílio à Pesquisa - Temático