Liquid biopsies to distinguish malignant from benign pulmonary nodules

Over the past decades, low-dose computed tomography (LD-CT) screening has been widely used for the early detection of lung cancer. Increasing numbers of indeterminate pulmonary nodules are now being discovered. However, it remains challenging to distinguish malignant from benign pulmonary nodules, especially those considered to be small or ground-glass (GGN) nodules. Liquid biopsies have been successfully applied in the diagnosis of advanced lung cancer, and the potential value for early detection of lung cancer has made great progress. Recent studies have demonstrated the value of various blood-based tumor biomarkers in determining the nature of pulmonary nodules, including cell-free DNA (cfDNA), microRNAs (miRNAs), circulating tumor cells (CTCs) and tumor-associated autoantibodies (AAbs). In this review, we summarize the latest progress of liquid biopsies, and their potential applications and challenges in the diagnosis of malignant pulmonary nodules.