Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE140082 | GEO | 2019/11/08
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: Recent progress in understanding the molecular biology of epithelial ovarian cancer has not yet translated into individualized treatment for these women or improvements in their disease outcome. Gene expression has been utilized to identify distinct molecular subtypes, but there have been no reports investigating whether or not molecular subtyping is predictive of response to bevacizumab in ovarian cancer.Experimental Design: DASL gene expression arrays were performed on FFPE tissue from patients enrolled on the ICON7 trial. Patients were stratified into four TCGA molecular subtypes. Associations between molecular subtype and the efficacy of randomly assigned therapy with bevacizumab were assessed.Results: Molecular subtypes were assigned as follows: 122 immunoreactive (34%), 96 proliferative (27%), 73 differentiated (20%), and 68 mesenchymal (19%). In univariate analysis patients with tumors of proliferative subtype obtained the greatest benefit from bevacizumab with a median PFS improvement of 10.1 months [HR, 0.55 (95% CI, 0.34-0.90), P = 0.016]. For the mesenchymal subtype, bevacizumab conferred a nonsignificant improvement in PFS of 8.2 months [HR 0.78 (95% CI, 0.44-1.40), P = 0.41]. Bevacizumab conferred modest improvements in PFS for patients with immunoreactive subtype (3.8 months; P = 0.08) or differentiated subtype (3.7 months; P = 0.61). Multivariate analysis demonstrated significant PFS improvement in proliferative subtype patients only [HR, 0.45 (95% CI, 0.27-0.74), P = 0.0015].Conclusions: Ovarian carcinoma molecular subtypes with the poorest survival (proliferative and mesenchymal) derive a comparably greater benefit from treatment that includes bevacizumab. Validation of our findings in an independent cohort could enable the use of bevacizumab for those patients most likely to benefit, thereby reducing side effects and healthcare cost. Clin Cancer Res; 23(14); 3794-801. ©2017 AACR.
| S-EPMC5661884 | biostudies-literature
Project description:Bevacizumab may differentially improve ovarian cancer outcome in patients with proliferative and mesenchymal molecular subtypes
| PRJNA588228 | ENA
Project description:Gene expression profiling was carried out for RNA extracted from Formalin-fixed, paraffin embedded (FFPE) biopsies for 172 patients with diffuse large b-cell lymphoma (DLBCL) using the Illumina DASL platform. Classification into GCB, ABC or Type-III subtypes was carried out revealing a significant relationship between subtype and survival.
2012-09-19 | GSE32918 | GEO
Project description:Formalin-fixed, paraffin-embedded (FFPE) samples of varying grade (II-IV) malignant gliomas were measured by Illumina cDNA-mediated Annealing, Selection, extension and ligration (DASL) platform. DASL platform was selected for its specialized design for partially degraded RNA.
2014-02-13 | GSE54004 | GEO
Project description:The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva; a humanized monoclonal antibody against circulating VEGF-A) when added to CCNU chemotherapy in recurrent GBM patients. In this study, we have performed gene expression profiling (DASL and RNA-seq) on formalin fixed, paraffin embedded (FFPE) tumor material from patients treated within the BELOB trial to identify recurrent GBM patients who benefit most from combined beva/CCNU treatment. We first extensively validate the use of FFPE tissues for expression profiling on both DASL and RNA-seq. Our data show that tumors assigned to IGS-18 or â??classicalâ?? GBMs show a significant benefit in progression free survival (PFS) and a trend towards benefit in overall survival (OS) from beva+CCNU treatment; other subtypes do not show such benefit. In particular, expression of FMO4 and OSBPL3 were associated with treatment response. All molecular glioma subtypes are evenly distributed along the different study arms and the improved outcome in the beva/CCNU arm therefore is not explained by an uneven distribution of prognostically favorable subtypes. Analysis of RNA-seq data highlighted genetic changes, including mutations, gene fusions (and identification of the exact genomic breakpoint), and copy number changes (albeit with limited resolution) within this well-defined cohort of tumors. When validated in an independent dataset, the predictive markers identified in this study will allow selection of recurrent GBM patients that benefit from beva+CCNU treatment. A total of 112 samples of patients included in the Belob trial were profiled. Profiling was done in three batches (3 raw data files; Belob1, Belob2 and Belob3*.txt). Please note that several replicates were performed to demonstrate platform reproducibility on FFPE material (basically the entire first experiment, samples 1-10 described in the all_sample_description.txt). In addition, a few samples were scraped (macrodissection) as the original tissue block contained a too low tumor content (as indicated in the sample description field). These Samples omitted from the final analysis are marked with X at the end of the patient ID column (in the all_sample_description.txt). Also, Of the 117 individual patients, the following patient samples were excluded in the final analysis: B11, B57, B73, B91 and B59. These samples were outliers in the gene expression analysis and did not meet the quality criteria (their median overall expression was <7.5 (log2)). The complete sample description and raw data (of 135 samples) are provided in the all_sample_description.txt and Belob*French.txt files, however only 112 samples (included in the final data analysis) are included in this record. Tumor Subtype (in the sample 'characteriscts) is defined by Gravendeel et al, Cancer Res 2009 Dec 1;69(23):9065-72. TCGA subtype (in the sample 'characteriscts) is defined by Verhaak et al, Cancer Cell. 2010 Jan 19;17(1):98-110. The sample 'chracteristic:Sensor' values indicate whether the patient alive or dead at time of analysis.
2016-01-19 | E-GEOD-72951 | biostudies-arrayexpress
Project description:The results from the randomized phase II BELOB trial provided evidence for a potential benefit of bevacizumab (beva; a humanized monoclonal antibody against circulating VEGF-A) when added to CCNU chemotherapy in recurrent GBM patients. In this study, we have performed gene expression profiling (DASL and RNA-seq) on formalin fixed, paraffin embedded (FFPE) tumor material from patients treated within the BELOB trial to identify recurrent GBM patients who benefit most from combined beva/CCNU treatment. We first extensively validate the use of FFPE tissues for expression profiling on both DASL and RNA-seq. Our data show that tumors assigned to IGS-18 or ‘classical’ GBMs show a significant benefit in progression free survival (PFS) and a trend towards benefit in overall survival (OS) from beva+CCNU treatment; other subtypes do not show such benefit. In particular, expression of FMO4 and OSBPL3 were associated with treatment response. All molecular glioma subtypes are evenly distributed along the different study arms and the improved outcome in the beva/CCNU arm therefore is not explained by an uneven distribution of prognostically favorable subtypes. Analysis of RNA-seq data highlighted genetic changes, including mutations, gene fusions (and identification of the exact genomic breakpoint), and copy number changes (albeit with limited resolution) within this well-defined cohort of tumors. When validated in an independent dataset, the predictive markers identified in this study will allow selection of recurrent GBM patients that benefit from beva+CCNU treatment.
2016-01-19 | GSE72951 | GEO
Project description:The use of Affymetrix U133 2.0 Plus chips on FFPE samples when coupled with a qPCR-based sample pre-assessment step, yielded satisfactory results from the point of view of biological reliability. When compared with the Illumina DASL WG platform, specifically designed for degraded RNA, the data generated with the Affymetrix platform showed a wider interquartile range (1.32 vs 0.57, p<2.2x10-16) suggesting a superior discriminatory power within samples as indicated by the good agreement with the immunohistiochemically derived ER status. FFPE primary breast cancer samples profiled using Illumina DASL WG platform after RNA amplification with the Nugen WT-Ovation FFPE System
2015-02-25 | GSE51451 | GEO
Project description:Gene expression profiling was carried out for RNA extracted from Formalin-fixed, paraffin embedded (FFPE) biopsies for 172 patients with diffuse large b-cell lymphoma (DLBCL) using the Illumina DASL platform. Classification into GCB, ABC or Type-III subtypes was carried out revealing a significant relationship between subtype and survival. A retrospective study of 172 patients, 140 treated with R-CHOP, 32 not treated with curative intent
2012-09-19 | E-GEOD-32918 | biostudies-arrayexpress
Project description:Formalin-fixed, paraffin-embedded (FFPE) samples of varying grade (II-IV) malignant gliomas were measured by Illumina cDNA-mediated Annealing, Selection, extension and ligration (DASL) platform. DASL platform was selected for its specialized design for partially degraded RNA. Overall mRNA was extracted from FFPE samples using the GoldenGate Assay protocol and hybridized to Illumina BeadChips.
2014-02-13 | E-GEOD-54004 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE32488: Expression profiling of formalin-fixed, paraffin-embedded (FFPE) breast cancer metastases of the lymph node and autopsy tissues [DASL HT-12 samples] GSE32489: Expression profiling of formalin-fixed, paraffin-embedded (FFPE) breast cancer metastases of the lymph node and autopsy tissues [DASL HumanRef-v3 samples] Refer to individual Series
2012-10-02 | E-GEOD-32490 | biostudies-arrayexpress