Current Evidence Supporting the Role of miRNA as a Biomarker for Lung Cancer Diagnosis Through Exhaled Breath Condensate Collection: A Narrative Review

Lung cancer, the leading cause of cancer-related mortality, has brought exhaled breath condensate (EBC) into focus as a promising non-invasive sample for detecting molecular biomarkers, particularly microRNAs, which regulate gene expression and contribute to tumorigenesis. Ten key studies encompassing approximately 866 subjects consistently demonstrated distinct patterns of miRNA dysregulation in lung cancer. Notably, several reported panels achieved diagnostic sensitivity and specificity exceeding 75% through the identification of distinct miRNA signatures in EBC, with oncogenic miRNAs (e.g., miR-21) upregulated and tumor-suppressor miRNAs (e.g., miR-486) downregulated in lung cancer patients. Analytical advancements, including next-generation sequencing (NGS), have improved miRNA detection sensitivity and specificity, addressing prior limitations of low yield and variability. NGS enabled the identification of novel miRNAs and proved especially effective in overcoming the low RNA yield associated with EBC samples. However, challenges persist regarding standardization of collection, sample dilution, and potential contamination. Moreover, the reproducibility of miRNA signatures across diverse patient populations remains a critical issue. Large-scale, multicenter validation studies are needed to establish robust diagnostic algorithms integrating EBC-derived miRNAs with existing clinical tools. The potential of EBC miRNA profiling to support current screening strategies could significantly improve early lung cancer detection and patient outcomes. Nevertheless, its clinical transition requires further methodological optimization and biomarker validation. This review critically evaluates current evidence on miRNA detection in EBC for lung cancer diagnosis.