0
0
Baltimore, MD – January 17, 2025: Researchers at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins University School of Medicine have unveiled a groundbreaking biomarker algorithm that may revolutionize the early detection of esophageal cancer and precancerous conditions like Barrett’s esophagus (BE). This innovative method, coupled with a noninvasive esophageal cell collection technique, could transform clinical screening practices.
Currently, diagnosing BE and esophageal cancer relies on invasive endoscopy procedures performed under anesthesia. The new approach, detailed in the American Journal of Gastroenterology, could potentially serve as a reflex test, guiding clinicians on when endoscopy is necessary for definitive diagnosis.
A Rigorous Path to Discovery
Led by Dr. Stephen Meltzer, a professor of medicine and oncology at Johns Hopkins, the study utilized a systematic process to identify biomarkers specific to BE, esophageal adenocarcinoma, and high-grade dysplasia. The algorithm incorporates methylation markers from genes such as USP44, TBC1D30, and NELL1, previously linked to various cancers.
“Methylation is a chemical modification that can affect gene expression and potentially drive cancer development,” explained Dr. Meltzer. “Our work marks the first study to identify biomarkers for these conditions using such a rigorous process.”
Innovative Sampling Technique
The noninvasive method involves swallowing a small sponge compressed in a gelatin capsule. Once in the esophagus, the capsule dissolves, allowing the sponge to expand and collect cells as it is pulled out via an attached string. Researchers then analyze these cells for abnormal methylation patterns.
This technique was tested on 234 esophageal sponge samples from patients with varying conditions, including BE, high-grade dysplasia, and esophageal adenocarcinoma. The study cohort represented a diverse group, with a median age of 65 and 66% male participation.
Promising Results
Using the data, researchers developed a three-biomarker algorithm that incorporated age and sex. This model achieved an exceptional diagnostic accuracy, with an area under the curve (AUC) of nearly 0.97 for distinguishing healthy tissue from esophageal cancer or high-grade dysplasia. For identifying BE and associated conditions, the algorithm demonstrated an AUC of 0.86.
“The goal of this test is not definitive diagnosis but to flag patients who may need further investigation with endoscopy,” Dr. Meltzer emphasized.
Implications for Global Health
Esophageal cancer, the eighth most common cancer worldwide, has seen a fivefold increase in incidence in Western populations over the past 40 years. It is a leading cause of cancer-related deaths, making early detection critical. Studies estimate that 5–12% of individuals with gastroesophageal reflux disease (GERD) may have undiagnosed BE, underscoring the importance of enhanced screening tools.
Dr. Meltzer expressed hope that large-scale studies could validate the algorithm and expand its use. “This research provides strong momentum for applying these markers in broader screenings, potentially improving survival rates for patients with Barrett’s esophagus and esophageal adenocarcinoma.”
Future Directions
The study, authored by Andrew Kalra and colleagues, highlights the potential of DNA methylation biomarkers in nonendoscopic detection of gastrointestinal conditions. Further validation and integration into clinical practice could herald a new era in early cancer detection, offering less invasive and more accessible diagnostics to patients worldwide.
Journal Reference:
Kalra, A., et al. “Discovery of Methylated DNA Biomarkers for Potential Non-Endoscopic Detection of Barrett’s Esophagus and Esophageal Adenocarcinoma,” American Journal of Gastroenterology (2025). DOI: 10.14309/ajg.0000000000003323
