Genomic signature of the standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography in breast cancer
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PROVIDER: PRJNA544730 | ENA |
REPOSITORIES: ENA
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Project description:The standardized uptake value (SUV), an indicator of the glucose uptake degree in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), has been used as a prognostic factor in malignant tumors. We aimed to identify a signature reflecting prognostic SUV characteristics in breast cancer (BRC). Transcriptome profiling was performed to identify a signature associated with the SUV in BRC patients who underwent preoperative FDG-PET. We defined a signature consisting of 723 genes significantly correlated with the SUV (|r| > .35; P < .001). The patient subgroups classified by the signature were significantly similar to those classified by the SUV (odds ratio, 8.02; 95% CI, 2.45 to 29.3; P < 0.001). The SUV signature showed independent clinical utility for predicting BRC prognosis (hazard ratio, 1.25; 95% CI, 1.11 to 1.42; P < 0.001). Integrative analysis demonstrated a significance of the signature in predicting the response to immunotherapy and revealed that a signaling axis defined by TP53-FOXM1 and its downstream effectors in glycolysis-gluconeogenesis, including LDHA, might be important mediators in the FDG-PET process. Our results reveal characteristics of glucose uptake captured by FDG-PET, supporting an understanding of glucose metabolism as well as poor prognosis in BRC patients with a high SUV.
2020-03-18 | GSE131769 | GEO
Project description:The standardized uptake value (SUV), an indicator of the glucose uptake degree in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), has been used as a prognostic factor in malignant tumors. We aimed to identify a signature reflecting prognostic SUV characteristics in triple negative breast cancer (TNBC). Transcriptome profiling was performed to identify a signature associated with the SUV in TNBC patients who underwent preoperative FDG-PET. We defined a signature significantly associated with the SUV (|r| > .35; P < .01). The SUV signature showed independent clinical utility for predicting BRC prognosis. Integrative analysis demonstrated a significance of the signature in predicting the response to immunotherapy and revealed that a signaling axis defined by TP53-FOXM1 and its downstream effectors in glycolysis-gluconeogenesis, including LDHA, might be important mediators in the FDG-PET process. Our results reveal characteristics of glucose uptake captured by FDG-PET, supporting an understanding of glucose metabolism as well as poor prognosis in TNBC patients with a high SUV.
2020-03-18 | GSE135565 | GEO
Project description:Gene expression profiles of the standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography in tripple negative breast cancer
| PRJNA559323 | ENA
Project description:Positron emission tomography (PET) is a nuclear medicine procedure based on the measurement of positron emission from radiolabelled tracer molecules. These radiotracers allow biologic processes to be measured and whole body images to be obtained which demonstrates sites of radiotracer accumulation. The most common radiotracer in use today is 18F-fluorodeoxyglucose (18F-FDG) which is a radiolabelled sugar (glucose) molecule. Imaging with 18F-FDG PET is used to determine sites of abnormal glucose metabolism and can be used to characterize and localize many types of tumours.
Cancer treatment and outcome depend largely on the accurate diagnosis and staging of disease. There is extensive data in the literature indicating the importance of FDG-PET imaging in accurately characterizing disease, as well as determining stage and sites of recurrent disease in many cancer types. For these indications, functional imaging with PET provides unique information which is not available from standard medical imaging modalities such as ultrasound, X-ray, computerized tomography (CT) or magnetic resonance imaging (MRI).
The objectives of this study are to document the safety and efficacy of 18F-FDG produced by the British Columbia Cancer Agency (BCCA) at its Tri-University Meson Facility (TRIUMF) production facility and to evaluate FDG-PET as a diagnostic and decision making tool in the management of oncology patients in British Columbia. With a population base of over 4 million people, standardized cancer treatment protocols, and evidence based guidelines for FDG-PET imaging, the BCCA is positioned to make an important contribution to defining the role of PET in the Canadian health care system.
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Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer.
2011-11-01 | GSE21217 | GEO
Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.
2011-11-01 | E-GEOD-21217 | biostudies-arrayexpress
Project description:We used a positron emission tomography (PET) tracer 18F fluorodeoxyglucose ([18F]-FDG) and transcriptomic analysis to detect glucose uptake by cells in the bone marrow micro-environment with an MLL-AF9-induced mouse model. Leukaemic cells had the greatest glucose uptake. To determine whether glucose uptake is driven by intrinsic demand, we applied RNA-seq of sorted leukaemia cells (GFP+) and bone marrow micro-environment myeloid cells (GFP-CD11b+) from the MLL-AF9 transduced mouse model.
2023-04-14 | GSE227581 | GEO
Project description:Differential gene expression between naive and activated CD8+ T cells was assessed using microarray analysis to determine target genes for new positron emission tomography (PET) probe screening, in particular for molecular imaging of lymphoid organs and immune activation. Keywords: cell activation comparison
2008-01-15 | GSE9997 | GEO
Project description:Type I interferons (IFNs) are critical effectors of emerging cancer immunotherapies designed to activate pattern recognition receptors (PRRs). A challenge in the clinical translation of these new immuno-modulatory agents is the lack of pharmacodynamic biomarkers indicative of increased intratumoral IFN signaling following PRR activation. Positron emission tomography (PET) imaging enables the visualization of tissue metabolic activity but whether IFN signaling-induced alterations in tumor cell metabolism can be detected using PET has not been investigated. We found that IFN signaling augments pancreatic ductal adenocarcinoma (PDAC) cell nucleotide metabolism via transcriptional induction of metabolism-associated genes including thymidine phosphorylase (TYMP). TYMP catalyzes the first step in the catabolism of thymidine which competitively inhibits intratumoral accumulation of the nucleoside analog PET probe [18F]-fluorothymidine ([18F]FLT). Accordingly, IFN treatment stimulates cancer cell [18F]FLT uptake in the presence of thymidine and this effect is dependent on TYMP expression. In vivo, genetic activation of stimulator of interferon genes (STING), a PRR widely expressed in PDAC, enhances the [18F]FLT avidity of xenograft tumors. Treatment with a small molecule STING agonist triggers IFN signaling-dependent TYMP expression in PDAC cells and enhances both subcutaneous and orthotopic tumor [18F]FLT uptake in vivo following systemic treatment. These findings indicate that [18F]FLT accumulation in tumors is sensitive to IFN signaling and that [18F]FLT PET may serve as a novel pharmacodynamic biomarker for PRR agonist-based immunotherapies in PDAC and possibly other malignancies characterized by elevated STING expression.
2021-08-30 | GSE178901 | GEO
Project description:Molecular imaging with positron emission tomography (PET) using [18F] fluorodeoxyglucose (FDG) has been suggested as an early, sensitive marker of tumour response to anticancer drugs by monitoring the changes in glucose metabolism in tumours. Recently, FDG-PET has shown to be highly sensitive in detecting early response in other tumours. In this study, the investigators will prospectively investigate the role of early FDG-PET (at day 7 and week 6) in outcome prediction.
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