A Dual-Marker DNA Methylation Assay Enables High-Sensitivity Detection of Malignant Effusions Across Cancer Types

Abstract

Simple Summary Distinguishing malignant from benign pleural and peritoneal effusions is essential for cancer diagnosis and treatment, but routine cytology often fails to detect malignant cells. We evaluated a DNA methylation test based on two cancer-related genes, SHOX2 and RASSF1A, in 696 patients with pleural or peritoneal effusions. The test showed higher sensitivity than conventional cytology while maintaining high specificity, and combining the two methods further improved diagnostic accuracy across multiple cancer types. The assay was particularly useful for identifying cancers that were missed or considered uncertain by cytological examination. These findings suggest that dual-gene DNA methylation testing is a reliable and minimally invasive tool that can complement routine pathology, improve the diagnosis of malignant effusions, and support earlier clinical decision-making for patients with cancer.