Epigenetic Changes as a Biomarker in African Americans with Papillary Renal Cell Carcinoma and a Link to the Tumor Microenvironment
Abstract
Our project seeks to evaluate features of epigenetics in papillary renal cell carcinoma (pRCC) and if they can be used as a blood-based biomarker for disease recurrence and if African American patients harbor unique changes relative to European ancestry patients. Epigenetics literally means above or on top of genetics. It denotes alterations to DNA that turn genes on or off. These modifications do not change the DNA sequence, but instead, they affect how cells read genes. One of the most common way cells make this modification is through methylation. While these changes are a normal biological phenomenon in how cells grow and divide, they can become pathologically altered in cancer states. In fact, these changes can be so characteristic of a tumor type that these marks be used as a method to detect tumor DNA from normal DNA. One of the main objectives of this study is to evaluate the detection of these tumor DNA epigenetic changes as a possible blood-based biomarker that could improve detection and sensitivity of recurrence above current standards that require frequent and less specific CT/MRI imaging. Though surgery can be curative for some of these patients, there is a high risk of disease recurrence for those with pRCC tumors. In the first part of this proposal, we will test the performance of a molecular assay to detect candidate methylation markers levels in the plasma (a component of blood) of patients with pRCC. This test is also known as a liquid biopsy. Our initial testing has demonstrated the ability of our assay to identify these candidate methylation markers in the plasma of pRCC patients. We will evaluate detection levels of these markers in a prospective group of patients before and after surgery or tumor ablation, both of which will be performed as curative treatment. By detecting whether any, or all, of the markers are still present in the patient s plasma after treatment, we believe we will be able to identify patients with early disease recurrence (before radiographic imaging can detect recurrence). Such patients could be ideally suited for altered surveillance protocols (i.e., more frequent) or possible adjuvant treatment in the context of a clinical trial. This method is like how persistent prostate-specific antigen levels are used as a sign of disease recurrence after prostate cancer treatment. We will also examine if the presence of these markers in patient blood can serve as a surrogate for changes and features in the tumor itself (i.e. the tumor microenvironment). An important feature of our study will also focus on African American patients as these patients have increased risk of pRCC and worse clinical outcomes even when controlling for things like pathological stage. The biological rationale for why these patients are at more risk and have worse outcomes is not understood and our study will examine if epigenetic changes could be a contributing factor. In line with the Congressional Metastatic Cancer Task Force, our study seeks to fill a gap in the care of these patients by developing practical liquid biopsy test for patients with pRCC. With respect to our project s ability to impact current kidney cancer patients, we have both short-term (1-2 years) and long-term (3-6 years) objectives. In the short term, we hope to validate and incorporate the use of these methylation markers to identify patients with early disease recurrence after presumed curative treatment. We also hope to have a liquid biopsy test that can inform clinicians and researchers about a patient s tumor features without the need for invasive tissue biopsies. The results of this study will focus on the difference between epigenetic markers between African American patients and their tumors compared to those from European ancestry. In the long term, these markers could also be evaluated as a screening test for patient without a diagnosis of pRCC, especially among groups at higher risk of dev
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310883
Entities
People
- Liang Wang
Organizations
- H. Lee Moffitt Cancer Center & Research Institute
- United States Army