Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

03-311 Trastzumab preoperative Trial of Early Stage HER2+ BRCA

ABSTRACT: Tumor core biopsies were obtained at baseline and after brief-exposure to single-agent trastuzumab from patients enrolled on the 03-311 trial. Gene expression profiling was conducted on these tumor biopsies to identify signatures of response to preoperative therapy. This study was initiated to identify biomarkers of response to preoperative trastuzumab-conotaining therapy. We performed transcriptional profiling of patient tumor biopsies obtained at baseline and post brief-exposure to trastuzumab to test the hypothesis that transcriptional changes upon brief-exposure to therapy can provide an early readout of subsequent response. A total of 50 patients generated quality microarray data at both both baseline and post-exposure timepoints. These 100 samples were analyzed for changes in immune subsets and pathway activities that correlated with subsequent response at surgery. Clinical response was assessed at the completion of preoperative therapy. Pathologic complete response (pCR) was scored by institutional pathologists and was defined as the absence of residual invasive disease in both the breast and any sampled axillary nodes; patients who failed to achieve pCR were grouped as objective responders (OBJR) category, which included complete and partial response (CR+PR), and non-responders (NOR) category including stable and progressive disease.

ORGANISM(S): Homo sapiens

SUBMITTER: Vinay Varadan

PROVIDER: E-GEOD-76360 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer.

Varadan Vinay V Gilmore Hannah H Miskimen Kristy L S KL Tuck David D Parsai Shikha S Awadallah Amad A Krop Ian E IE Winer Eric P EP Bossuyt Veerle V Somlo George G Abu-Khalaf Maysa M MM Fenton Mary Anne MA Sikov William W Harris Lyndsay N LN

Clinical cancer research : an official journal of the American Association for Cancer Research 20160203 13

<h4>Purpose</h4>Recent data suggest that intrinsic subtype and immune cell infiltration may predict response to trastuzumab-based therapy. We studied the interaction between these factors, changes in immune signatures following brief exposure to trastuzumab, and achievement of pathologic complete response (pCR) to subsequent preoperative trastuzumab and chemotherapy in HER2-positive breast cancer.<h4>Experimental design</h4>In patients enrolled on two multicenter trials (03-311 and 211B), tumor ...[more]

PMID: 26842237

Similar Datasets

Project description:Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional role of senataxin in disease, we examined differential gene expression in AOA2 patient fibroblasts, identifying a core set of genes showing altered expression by microarray and RNA-sequencing. To determine whether AOA2 and ALS4 mutations differentially affect gene expression, we overexpressed disease-specific SETX mutations in senataxin-haploinsufficient fibroblasts and observed changes in distinct sets of genes. This implicates mutation-specific alterations of senataxin function in disease pathogenesis and provides a novel example of allelic neurogenetic disorders with differing gene expression profiles. Weighted gene co-expression network analysis (WGCNA) demonstrated these senataxin-associated genes to be involved in both mutation-specific and shared functional gene networks. To assess this in vivo, we performed gene expression analysis on peripheral blood from members of 12 different AOA2 families and identified an AOA2-specific transcriptional signature. WGCNA identified two gene modules highly enriched for this transcriptional signature in the peripheral blood of all AOA2 patients studied. These modules were disease-specific and preserved in patient fibroblasts and in the cerebellum of Setx knockout mice demonstrating conservation across species and cell types, including neurons. These results identify novel genes and cellular pathways related to senataxin function in normal and disease states, and implicate alterations in gene expression as underlying the phenotypic differences between AOA2 and ALS4. Total RNA samples obtained from 1) an AOA2 patient and carrier fibroblast cell lines, 2) 2 biological replicates of haploinsufficient SETX fibroblast cell lines transfected with one of 4 different wild-type and mutant SETX constructs, 3) peripheral blood from 33 patients and carriers across 12 families, and 4) 2 tissues from 2 Setx knockout and 2 control mice were analyzed using expression microarray. This submission represents the microarray component of study.

Dataset Information

03-311 Trastzumab preoperative Trial of Early Stage HER2+ BRCA

Publications

Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets