Unlocking the diagnostic and prognostic potential of 5HMC in urine cfdna: characterization of genome-wide landscape in healthy urine and biomarker development in localized bladder cancer
Active Project Grant Awarded Last action
- Award ID
- F30CA288116
- Recipient
-
The University Of Chicago UEI ZUE9HKT2CLC9
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $324,268
Award facts
- Assistance listing
- 93.398 Cancer Research Manpower
- Completion date 60% complete
- Place of performance
- Chicago, IL 60637, USA
Award details come from USAspending.gov.
Description
- Abstract
- Epigenetic modifications play a crucial role in mammalian development, cellular differentiation, and disease, with 5-methylcytosine (5MC) being the most well-studied epigenetic modification. 5MC globally represses gene expression and has significant gene-regulatory importance in various diseases. The ten-eleven translocation (TET) family of enzymes can oxidize 5MC to 5-hydroxymethylcytosine (5HMC), which is a stable marker of global transcriptional activation. While previous studies have characterized the role of 5HMC modifications in healthy human tissues and evaluated plasma cell-free DNA (cfdna) for its biomarker potential in various malignancies, urine cfdna has not yet been studied. Urine represents a non-invasive, easily collectible, and proximal biofluid to a number of GU diseases. At present, IT is unclear how urine cell-free DNA (cfdna) 5HMC profiles reflect normal physiological conditions and mirror the composition of neighboring tissues. Researchers wonder whether urine cfdna 5HMC profiles might offer a superior alternative to plasma cfdna, the current gold standard in liquid biopsy, in the diagnosis of GU cancers like bladder cancer. To address these questions, this proposal seeks to characterize the genome-wide 5HMC landscape of healthy urine and develop biomarkers in the setting of localized bladder cancer. The proposal aims to achieve these objectives through two specific aims. The first aim focuses on identifying sources of unwanted variation, characterizing the genomic and epigenomic 5HMC landscape, and inferring the tissue-of-origin of cell-free DNA (cfdna) derived from healthy urine samples. To accomplish this aim, a bioinformatic pipeline will be optimized for processing 5HMC profiles from urine cfdna. The 5HMC regulation in urine cfdna will be characterized by analyzing its activity on gene bodies, promoters, enhancers, and various regulatory epigenomic regions. This aim also proposes the creation of tools to determine the tissue-of-origin of urine cfdna and confirm its enrichment for GU tissues compared to plasma cfdna, highlighting the applicability of urine cfdna in GU contexts. The insights gained from aim 1 will provide a reference for evaluating the deviations in 5HMC distribution in urine cfdna in various cancer and non-cancer disease states. The second aim focuses on developing robust diagnostic and predictive biomarkers for localized bladder cancer. The study will demonstrate the utility of urine cfdna 5HMC-profiles in bladder cancer diagnosis and treatment surveillance and compare its performance to plasma cfdna 5HMC profiles. Additionally, a multi- omics classifier model incorporating 5HMC, copy number, and targeted mutational data will be created and validated for predicting minimal residual disease in bladder cancer patients who underwent curative-intent bladder removal surgery. The results from aim 2 will generate 5HMC signatures that can be used to predict the onset of localized bladder cancer and to predict minimal residual disease. Ultimately, the data from aim 2 could deliver a set of new gene and enhancer targets that maybe serve as exciting therapeutic targets for prevenation and treatment of bladder cancer.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $576 | |
| Amendment | $54,538 | |
| Amendment | $54,538 | |
| Amendment | $1,280 | |
| Amendment | $0 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $0 | |
| Amendment | $52,694 | |
| Amendment | $52,694 | |
| Amendment | $52,694 | |
| Original award | $52,694 |
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Quick answers
Who received award F30CA288116?
F30CA288116 was awarded to The University Of Chicago by National Cancer Institute (National Institutes of Health) on August 6, 2024.
How much is award F30CA288116 worth?
$324,268 has been obligated on F30CA288116.
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