Pleural effusion (PE) is a common sign caused by various disorders. Microbiology, histology and cytology are reference standards for these disorders. However, these diagnostic tools have limitations, including invasiveness, high cost, long turnaround time, and observer-dependent. Soluble biomarkers in pleural fluid (PF) are promising diagnostic tools because they are mininvasive, economical, and objective. Recent studies have revealed that some cell-free nucleic acids (e.g., DNA, mRNA, microRNA, and lncRNA) in PF are potential diagnostic markers for many disorders. Here, we review the performance of PF cell-free nucleic acids for differentiating and stratification of PE.
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