Expression data from breast cancer FNA and surgical specimens from patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32072 | GEO | 2012/01/17
SECONDARY ACCESSION(S): PRJNA147597
REPOSITORIES: GEO
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Project description:The behavior of breast cancers and their response to neoadjuvant systemic therapy depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell. The purpose of the analysis was to compare matched gene expression profiles of pretreatment cancer with post-neoadjuvant systemic therapy, residual cancer. Pre-treatment FNA from primary tumors or post-treatment surgical specimens were obtained and RNA extracted and hybridized to afymetrix microarrays according to manufacturer protocol.
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Project description:The behavior of breast cancers and their response to neoadjuvant systemic therapy depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell. The purpose of the analysis was to compare matched gene expression profiles of pretreatment cancer with post-neoadjuvant systemic therapy, residual cancer. Pre-treatment FNA from primary tumors or post-treatment surgical specimens were obtained and RNA extracted and hybridized to afymetrix microarrays according to manufacturer protocol.
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Project description:The purpose of this study was to identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression profiling were done on pretreatment biopsies. Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR). Proteomic and validation immunohistochemical analyses revealed that α-defensins (DEFA) were overexpressed in tumors from patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated with response to therapy at the time of surgery. We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxane–based therapy.
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