Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

42 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profiling of biopsy and resection samples from the DEBIOC phase 1 trial of oxaliplatin and capecitabine +/- AZD8931 in oesophageal cancer

ABSTRACT: The Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC) trial reported an acceptable safety profile for neoadjuvant Oxaliplatin and Capecitabine (Xelox) +/- AZD8931 in oesophageal adenocarcinoma (OAC) but limited efficacy. We evaluated the impact of neoadjuvant Xelox +/-AZD8931 on biological pathways using a unique software-driven solution. Transcriptomic profiles from 25 pre-treatment FFPE OAC biopsies and 17 matched resection specimens, treated with Xelox+AZD8931 (n=16) and Xelox alone (n=9), were analysed using the Almac claraT total mRNA report. Tumour Infiltrating Lymphocytes (TILs) were assessed digitally using QuPath software. Hierarchical clustering identified three molecular subgroups classified by activation of innate immune signalling. The Immune High subgroup was associated with HER2 positivity, increased pathological response and a marked reduction in immune signalling and TILs following neoadjuvant therapy. The Immune Low cluster was pre-dominantly HER2/EGFR negative and EGFR positivity was associated with the Immune Mixed subgroup. Neoadjuvant therapy induced angiogenesis and EMT signalling and a reduction in DNA repair signatures with AZD8931 also promoting an immunosuppressive microenvironment. OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2 positive/Immune High tumours.

ORGANISM(S): Homo sapiens

SUBMITTER: Richard Turkington

PROVIDER: E-MTAB-13741 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer

Project description:The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors. Fresh frozen tumor samples obtained by vacuum-assisted core biopsy from one hundred and fifteen patients were subjected to RNA extraction and hybridization on Affymetrix microarrays.

2012-03-20 | E-GEOD-32646 | biostudies-arrayexpress

Gene expression profiling of 60 pre-chemotherapy FFPE endoscopic oesophageal adenocarcinoma biopsies

Project description:Oesophageal cancer is the ninth most common cancer in the UK and accounts for 5% of all cancer deaths. The incidence of the disease in men has risen 50% in the last 25 years with the commonest pathological subtype in the West being adenocarcinoma, while in East Asia oesophageal squamous cell carcinoma predominates. Despite efforts to screen for Barrett’s oesophagus, and pre-operatively select OAC patients who are likely to benefit from potentially curative surgery, survival remains poor. The five year survival rate is less than 17% and even in early stage locoregional confined disease this figure lies between 25-35%. A significant improvement in overall survival has been demonstrated with neo-adjuvant or peri-operative chemotherapy but the optimal approach for individual patients remains unclear. A consistent finding has been that complete histopathological response to neo-adjuvant chemotherapy is a prognostic biomarker for increased survival benefit. Therefore, there is a pressing need to identify biomarkers capable of predicting response, enabling clinicians to select patients for whom neo-adjuvant therapies would be beneficial. This experiment represents gene expression profiling of 60 pre-treatment formalin-fixed paraffin embedded (FFPE) oesophageal adenocarcinoma biopsies. All patients were treated with neo-adjuvant cisplatin-based chemotherapy prior to surgical resection at the Northern Ireland Cancer Centre from 2004-2012. The aim of the experiment was to carry out functional enrichment of pathological responders and non-responders to neo-adjuvant chemotherapy in order to identify novel mechanism of drug resistance or chemo-sensitivity.

2018-05-10 | E-MTAB-4666 | biostudies-arrayexpress

Validation cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer

Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant validation cohort of 198 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.

2011-05-11 | E-GEOD-25065 | biostudies-arrayexpress

Discovery cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer

Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant study of 310 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.

2011-05-11 | E-GEOD-25055 | biostudies-arrayexpress

HER2-enriched tumor initiating cell (HTIC) genomic predictor of response following neoadjuvant trastuzumab-based chemotherapy in HER2+ breast cancer

Project description:We identified a 17-gene Her2-enriched tumor initiating cell (HTIC) signature in MMTV-Her2/Neu mouse mammary TICs. Here, we show that patients with HTICS+ HER2+:ERα− tumors are more likely to achieve a pathologic complete response to trastuzumab-based neoadjuvant chemotherapy compared with HER2+:ER+ tumors. Neoadjuvant study of 50 HER2-positive breast cancer cases treated with trastuzumab-based chemotherapy pre-operatively. Pre-treatment FNA from primary tumors were obtained and RNA extracted and hybridized to Affymetrix microarrays according to manufacturer protocol. Pathologic response was assessed at the end of neoadjuvant treatment.

2012-05-11 | E-GEOD-37946 | biostudies-arrayexpress

ColXα1 and Tumor Infiltrating Lymphocytes: a Marker of Response to Neoadjuvant Therapy in Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer

Project description:This study focused on patients with estrogen receptor positive/human epidermal growth factor receptor 2 positive (ER+/HER2+) breast cancer treated with neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel biomarkers by correlating gene expression, histology and immunohistochemistry with pathologic response. We performed gene expression profiling on 11 pre-treatment tumors samples: 5 who had no or minimal residual disease residual cancer burden (RCB) score of 0 or 1 and 6 who had significant residual disease (RCB score of 2 or 3). ER2/HER2 postive breast tumors biopsied before neoadjuvant chemotherapy were selected to identify potential biomarkers of pathological complete response (pCR)

2015-09-08 | E-GEOD-67982 | biostudies-arrayexpress

Profiling of pancreatic adenocarcinoma using artificial intelligence-based integration of multi-omic and computational pathology features

Project description:Contemporary analyses focused on a limited number of clinical and molecular features have been unable to accurately predict clinical outcomes in pancreatic ductal adenocarcinoma (PDAC). Here we describe a novel, conceptual approach and use it to analyze clinical, computational pathology, and molecular (DNA, RNA, protein, and lipid) analyte data from 74 patients with resectable PDAC. Multiple, independent, machine learning models were developed and tested on curated singleand multi-omic feature/analyte panels to determine their ability to predict clinical outcomes in patients. The multi-omic models predicted recurrence with an accuracy and positive predictive value (PPV) of 0.90, 0.91, and survival of 0.85, 0.87, respectively, outperforming every singleomic model. In predicting survival, we defined a parsimonious model with only 589 multi-omic analytes that had an accuracy and PPV of 0.85. Our approach enables discovery of parsimonious biomarker panels with similar predictive performance to that of larger and resource consuming panels and thereby has a significant potential to democratize precision cancer medicine worldwide.

2024-01-23 | PXD037038 | Pride

Gene expression profiling in response to radiation treatment in human breast cancer

Project description:Treatment-related morbidities have been linked to the large post-operative treatment volumes required for external beam partial breast irradiation (PBI). Alternative PBI techniques require equipment that is not readily available. To address these issues, we designed a phase I trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Women 55 or older with clinically node negative, ER+ and/or PR+, HER2-, T1 invasive carcinomas or low-intermediate grade in situ disease â¤2cm were enrolled (n=32). Intensity-modulated radiotherapy was used to deliver 15 Gy (n=8, patients 01-08), 18 Gy (n=8, patients 09-16), or 21Gy (n=16, patients 17-32) to the tumor with a 1.5cm margin. Lumpectomy was performed within 10 days. Paired pre- and post-radiation MRI images and patient tumor samples were analyzed.

2015-10-31 | E-GEOD-65505 | biostudies-arrayexpress

A phase 1b study of the Akt-inhibitor MK-2206 in combination with weekly paclitaxel and trastuzumab in patients with advanced HER2-overexpressing solid tumor malignancies

Project description:16 patients with HER2+ tumors were enrolled (12 breast, 3 gastric, 1 esophageal). 27 samples (12 primary + 15 metastatic) from the 16 unique patients were assayed on Agilent 60K expression microarrays, and association between expression and response data were evaluated to identify potential biomarker of MK2206 response We conducted a phase 1b study of MK-2206 in combination with weekly paclitaxel 80 mg/m2 and trastuzumab 2 mg/kg in patients with HER2+ malignancies. Dose escalation was performed using a modified toxicity probability interval method. Molecular profiling of archived tissue samples and limited PK analyses were performed.

2016-07-31 | E-GEOD-75087 | biostudies-arrayexpress

Gene Expression Profiling of FFPE Pre-treatment Endoscopic Biopsies from Oesophageal Adenocarcinoma Patients Treated with Neo-adjuvant Chemotherapy and Surgical Resection

Project description:Gene expression profiling of 273 pre-treatment endoscopic FFPE oesophageal and oesophago-gastric junctional adenocarcinomas for validation of a DNA Damage Response Deficiency Assay. All patients were treated with neo-adjuvant chemotherapy followed by surgical resection and were collected at four UK centres in the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium between 2004 and 2013. Biopsies were reviewed for pathological subtype prior to marking for macrodissection and samples containing at least 50% adenocarcinoma tissue by area were taken forward. Total RNA was extracted using the RecoverallTM Total Nucleic Acid Isolation Kit for FFPE (Thermo Fisher Scientific, Waltham, MA) and amplified using the NuGen Ovation FFPE Amplification System v3 (NuGen San Carlos, CA). The amplified product was hybridized to the Almac Diagnostics Xcel™ array (Almac, Craigavon, United Kingdom), a cDNA microarray-based technology optimized for archival FFPE tissue, and analysed using the Affymetrix 7G scanner (Affymetrix, Santa Clara, CA)

2019-01-31 | E-MTAB-6969 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data