Validation of Methylated DNA Markers for Esophageal Squamous Cancer: An International Study

Esophageal squamous cell carcinoma (ESCC) remains a leading cause of cancer-related mortality worldwide and there are limited molecular screening options. Following a prior discovery and validation studies in subjects from the United States, China, and Iran, we aimed to validate methylated DNA markers (MDMs) for ESCC detection in Malawi, a country with one of the highest ESSC incidence. Fourteen MDMs were tested on 177 tissue samples. Ten MDMs showed excellent performance (AUCs ≥0.85); a random forest model achieved an AUC of 0.97. The consistent cross-population performance suggests potential for universal application of these MDMs and further justifies exploring non-endoscopic sampling methods, such as swallowed cell collection devices in combination with MDMs, for efficient and cost-effective screening in high-incidence populations.