GenomicScarsInTnbcs_AGrigoriadis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Anita Grigoriadis
PROVIDER: E-MTAB-2626 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Triple negative breast cancer (TNBC) is characterized by high proliferation, poor differentiation and a poor prognosis due to high rates of recurrence. Despite lower overall incidence African American (AA) patients suffer from higher breast cancer mortality in part due to the higher proportion of TNBC cases among AA patients compared to European Americans (EA). It was recently shown that the clinical heterogeneity of TNBC is reflected by distinct transcriptional programs with distinct drug response profiles in preclinical models. In this study, we used gene expression profiling and immunohistochemistry to eluicidate potential differences between TNBC tumors of EA and AA patients on a molecular level. WG-DASL experiment of 90 FFPE samples of ER, PR and HER2 (triple) negative breast cancer samples diagnosed between 1987 and 2007. Invasive disease was identified on H&E sections by the study pathologist and one to three 1.5 mm cores were punched from the top down in the designated tumor areas of each FFPE block. The cores were deparaffinized with xylene at 50°C for 3 minutes. RNA was extracted using the RecoverAll Total Nucleic Acid Isolation kit (Applied Biosystems) following the manufacturer's protocol. The isolated RNA was hybridized to Whole-Genome DASL (HumanRef8 V 3.0, Illumina) at the Yale Center for Genome Analysis. 90 primary tumor RNA samples from 90 patients were adequate for analysis and passed Quality control.
2013-08-15 | E-GEOD-46581 | biostudies-arrayexpress
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 taxaneâbased therapy. Tumor tissues from pretreatment needle biopsies from patients enrolled on a paclitaxel/radiation clinical trial were laser capture microdissected for RNA extraction and hybridization to Affymetrix microarrays. We analyzed one array (sample A) from duplicate samples from each patient. 14 subject, 2 replicates each.
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