# Development of a highly sensitive DNA hypermethylation-based kit to identify Barrett's esophagus patients at high risk of progressing to esophageal adenocarcinoma

> **NIH NIH R41** · PRE-CANCER DIAGNOSIS, LLC · 2024 · $398,738

## Abstract

Summary
The incidence of esophageal adenocarcinoma (EAC) has increased 600-700% in North America since the
1980s. EAC only has 18-22% of an overall 5-year survival rate because most patients are discovered at an
advanced stage. The single major risk factor for the development of EAC is Barrett’s esophagus (BE) where
intestinal-like glandular epithelium replaces the normal squamous mucosa of the esophagus. BE affects
approximately 2-5.4%of the adult population in the United States, with 0.12% to 1.6% of BE patients progressing
to EAC annually. Most BE patients will not progress to EAC, but they will experience anxiety and fear about their
uncertain future. It is urgent to find biomarkers to identify BE patients at high-risk progressing to EAC. DNA
hypermethylation at specific genes is the best indicator and occurs early in tumorigenesis and typically increases
with tumor progression. Recently, the role of epigenetic change in the pathogenesis of BE and EAC were
extensively studied. Multiple methylation markers have been suggested to discriminate between high -risk and
low risk BE. However, the sensitivity is relatively low for clinically predicting the patients at high-risk of
progressing to EAC. Regardless of these methylation studies, the clinically useful methylation biomarkers for
predicting BE patients to progress to EAC are still missing. Pre-Cancer Diagnosis is working to address this
critical unmet need by developing a sensitive diagnostic test that will use a target DNA hypermethylation panel
to identify those BE patients with the high-risk progressing to EAC. Recently, we found that several genes with
DNA hypermethylation could identify high-risk BE patients that are progressing to EAC, which demonstrated an
extremely high sensitivity (≈100%), and specificity (≈100%). With the DNA methylation test, we could triage the
BE patients into high-risk and low-risk groups: the high-risk patients will receive early treatment including
mucosal resection or radiofrequency ablation; the low-risk patients will have a longer follow-up interval, which
will decrease the cost. The objective of this study is to validate our preliminary data and further develop a new
methylation diagnostic kit to predict high-risk BE progression to EAC. In Aim 1, we will validate the
hypermethylation genes and develop a methylation diagnostic kit that differentiate BE patients with and without
a high risk of progressing to EAC by both DNA Methylation Epic array and PCR methylation tests. In Aim 2. We
will use whole genome sequence to validate the methylation genes that can predict high -risk BE patients
progressing to EAC and then we will develop a Target Methylation panel (a diagnostic kit) for the clinical trial.
This test will identify high-risk BE patients before progressing to EAC, which is crucial for reducing the incidence
of EAC and improving patient outcomes.

## Key facts

- **NIH application ID:** 10919150
- **Project number:** 1R41CA291354-01
- **Recipient organization:** PRE-CANCER DIAGNOSIS, LLC
- **Principal Investigator:** Zhongren Zhou
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $398,738
- **Award type:** 1
- **Project period:** 2024-09-04 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919150

## Citation

> US National Institutes of Health, RePORTER application 10919150, Development of a highly sensitive DNA hypermethylation-based kit to identify Barrett's esophagus patients at high risk of progressing to esophageal adenocarcinoma (1R41CA291354-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10919150. Licensed CC0.

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