Analysis of pleural fluid biomarkers for diagnosis of malignant pleural effusion and molecular characterization of lung cancer: a review.

PURPOSE OF REVIEW: Malignant pleural effusion (MPE) is a common complication of advanced lung cancer and often represents the first sign of malignancy. Conventional diagnostic methods, including cytology and pleural biopsy, have limited sensitivity. This review provides a timely assessment of emerging pleural fluid biomarkers and their utility in differentiating malignant from benign effusions, as well as their role in guiding molecular characterization of lung cancer to improve diagnostic accuracy and therapeutic decision-making.

RECENT FINDINGS: Recent studies highlight the diagnostic and molecular profiling potential of circulating tumor DNA (ctDNA), microRNAs, proteins, and metabolites detectable in pleural fluid. Advances in next-generation sequencing and liquid biopsy technologies have enabled noninvasive detection of actionable mutations (EGFR, ALK, KRAS, PD-L1), enhancing molecular profiling directly from pleural samples. Integration of multiple biomarkers shows promise for improving sensitivity and specificity compared to cytology alone.

SUMMARY: Pleural fluid biomarker analysis offers a minimally invasive, clinically relevant approach for diagnosing MPE and identifying molecular targets in lung cancer. Further standardization and validation of testing protocols are needed, but these advances hold potential to refine early diagnosis, guide targeted therapies, and personalize management strategies for patients with lung cancer-related effusions.