Development and validation of a plasma miRNA-CEA biomarker panel for early detection of lung cancer

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, underscoring the critical need for early detection to improve patient outcomes. This study aimed to develop and validate a plasma microRNA (miRNA) biomarker panel for the early detection of non-small cell lung cancer (NSCLC) in a Japanese cohort. We enrolled 525 participants, comprising 261 LC cases and 264 non-LC controls, divided into optimization and validation cohorts. A 12-miRNA panel was optimized and further combined with carcinoembryonic antigen (CEA) to enhance diagnostic performance. The miRNA-alone model demonstrated robust performance in both the optimization (AUC = 77.0%) and validation cohorts (AUC = 75.3%). Integration with CEA significantly improved accuracy, achieving AUCs of 86.2% (optimization) and 84.9% (validation), with particularly high performance in late-stage cancers (AUC=94.4%) and squamous cell carcinoma (SCC) (AUC=90.7%). Sensitivity and specificity thresholds were evaluated, enabling model customization for diverse clinical scenarios. These findings highlight the potential of the miRNA-CEA panel as a minimally invasive tool for early LC detection, especially in non-smoking populations. Based on these results, we successfully developed the LUNGClear kit, the world’s first miRNA-based liquid biopsy for lung cancer, paving the way for future clinical application.