Liquid biopsy biomarkers for accurate detection of malignant pulmonary nodules: a meta-analytic approach.

UNLABELLED: Pulmonary nodules are a common radiological finding that can be classified as either benign or Malignant, with significant clinical implications. The early detection of malignant nodules is critically important for improving the prognosis of lung cancer, which remains the leading cause of cancer-related mortality worldwide. Traditional imaging techniques have Limitations in accurately classifying pulmonary nodules. Liquid biopsy, a minimally invasive method that evaluates circulating components in the Blood, presents promising diagnostic potential in this context. This study aims to evaluate the diagnostic capacity of multiple liquid biopsy biomarkers for early and accurate differentiation between benign and Malignant pulmonary nodules. Accordingly, we conducted a comprehensive study involving a meta-analysis, selecting 16 eligible studies that utilised liquid biopsy to assess various circulating biomarkers in the diagnostic yield. The most significant results were linked to circulating free DNA (cfDNA). However, other components, including circulating tumour cells (CTCs), microRNAs/pfeRNAs, extracellular vesicles (EVs), serological markers, and imaging techniques, also provided valuable information. Similarly, integrating multi-omics data with machine learning models has been shown to enhance the ability to differentiate between benign and malignant pulmonary nodules, thereby supporting early diagnosis and improved management for patients with lung cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-03646-1.