20200819_EGA_Qld_Melanoma.radiomics - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006375 | EGA |
REPOSITORIES: EGA
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Project description:BACKGROUND. Improving and predicting tumor response to immunotherapy remains challenging. Combination therapy with a transforming growth factor β (TGF-β) inhibitor that targets cancer associated fibroblasts (CAFs) is promising to enhance efficacy of cancer immunotherapies. However, the effect of this approach in clinical trials is limited, requiring in vivo methods to better assess tumor responses to combination therapy. METHODS. We measure CAFs in vivo using gallium 68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) for PET/CT imaging to guide TGF-β inhibition and sensitize metastatic colorectal cancer (CRC) to immunotherapy. A total of 131 patients with metastatic CRC underwent 68Ga-FAPI and 18F-fludeoxyglucose (18F-FDG) PET/CT imaging. Fourteen patients underwent surgery after the imaging. Relationship between uptake of 68Ga-FAPI and tumor immunity was analyzed. Mouse cohorts of metastatic CRC were treated with TGF-β receptor (TGF-βR) inhibitor combined with KN046 which blocks PD-L1 and CTLA4, followed with 68Ga-FAPI and 18F-FDG micro-PET/CT imaging to assess tumor responses. RESULTS. Patients with metastatic CRC demonstrated high uptakes of 68Ga-FAPI, along with suppressive tumor immunity and poor prognosis. TGF-βR inhibitor enhanced tumor infiltrating T cells and significantly sensitized metastatic CRC to KN046. 68Ga-FAPI PET/CT imaging accurately monitored the dynamical changes of CAFs and tumor response to combined TGF-βR inhibitor with immunotherapy. CONCLUSION. 68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to stratify and guide patients with CRC for precise TGF-β inhibition plus immunotherapy, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management.
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Project description:To rapidly identify new prognostic imaging biomarkers, we propose a bioinformatics approach that integrates gene expression and image data and leverages public gene expression data. We demonstrate our approach in non-small cell lung carcinoma patients for whom CT, PET/CT and gene expression data are available but without clinical follow-up. We extracted 180 image features and 56 high quality gene expression clusters, represented by metagenes. 115 image features were expressed in terms of metagenes, using sparse linear regression and cross-validation, with an accuracy of 65-86%. After mapping the signatures to a public gene expression dataset, 26 image features were significantly associated with recurrence-free survival and 22 with overall survival. A multivariate analysis identified multiple image features that were prognostic, independent of clinical covariates. Identifying prognostic imaging biomarkers by linking images and gene expression with outcomes in public gene expression datasets promises to accelerate the role of imaging in personalized medicine.
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Project description:Genome-wide methylation profiles were generated as part of a multi-omics characterization (SNP array, WES, RNA-seq, cDNA microarray) of a panel of gliomasphere cell lines and matched parental tumors. See https://www.ncbi.nlm.nih.gov/pubmed/27571888 about the GlioTeX panel. Methylation profiling data in this record come from tumour samples. SNP array (ArrayExpress E-MTAB-4804), cDNA microarray (ArrayExpress E-MTAB-4803), WES and RNAseq (European Genome-Phenome Archive EGAS00001001871) have been published before. In addition, for the current project we compare 450K methylation data to nanopore sequencing based methylation profiles. These sequencing data will be accessible via European Genome-Phenome Archive (EGAS00001002213). Please also refer to https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5795/files/E-MTAB05795.additional.1.zip for further information on the background of this multi-omics study.
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Project description:High-order rice chromatin contains numerous interactions among DNA, RNA and protein to regulate critical biological processes in various aspects of rice life. We developed an effective method for mapping histone-mediated chromatin associated RNA-DNA interactions, followed by paired-end-tag sequencing (ChRD-PET) in rice. With H3K4me3 ChRD-PET, H3 ChRD-PET and RNase H treated H3K4me3 ChRD-PET, we present a highly comprehensive map of RNA and chromatin interactions around promoters in rice MH63. Through integrating ChIA-PET (published data), ChRD-PET and ssDRIP-seq data analysis, we demonstrated the function of RNAs-chromatin interactions in different level. We also conducted ATAC-seq and integrative analysis uncovered the relationship of epigenetic modifications and ChRD-PET interactions. Our findings firstly revealed the map and features of RNAs-chromatin interactions in rice.
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