Abstract / Summary
Objective: This study evaluated the diagnostic value of a combined SHOX2 and RASSF1A methylation assay (LungMe®) in differentiating malignant from benign pleural and peritoneal effusions. Methods: A total of 696 patients with pleural or peritoneal effusions were prospectively enrolled. Effusion sediment samples were analyzed by liquid-based cytology (TCT), cell block histology, and methylation-specific PCR for both SHOX2 and RASSF1A. The final diagnosis was confirmed by clinical, imaging, and pathological follow-up. Results: Lung cancer was the predominant cause of malignant pleural effusions (71.96%), while malignant peritoneal effusions mainly resulted from ovarian, gastric, and liver cancers. The optimal ΔCt cutoffs for SHOX2 and RASSF1A were ΔCt ≤ 9 and ΔCt ≤ 12, respectively. The combined methylation assay achieved a sensitivity of 79.1% and specificity of 90.4% for malignant effusions. When combined with cytology, the overall sensitivity increased from 34.7% (TCT alone) to 91.7%, with a positive predictive value (PPV) of 93.9% and a negative predictive value (NPV) of 86.7%. The assay showed high sensitivity across multiple tumor types, including 100% for esophageal and breast cancers, and ≥80% for lung cancer, gastric cancer, lymphoma, and cholangiocarcinoma. Conclusions: The combined SHOX2 and RASSF1A methylation assay has high diagnostic value for benign–malignant discrimination of pleural and peritoneal effusions, improving diagnostic sensitivity when combined with conventional cytology. Thus, within the context of this single-center study, the LungMe® assay demonstrates promise in expanding pan-cancer diagnostics, but will require further multicenter external validation and prospective clinical studies before routine clinical adoption.