Blood-Based miRNA Panels for Timely Detection of Non-Small-Cell Lung Cancer: From Biomarker Discovery to Clinical Translation

Lung cancer (LC) remains a leading cause of global cancer mortality, driving the need for novel timely detection strategies, i.e., stages I-II detection when tumor curation is efficient. Circulating microRNA (miRNAs), with their unique stability in biofluids, offer a powerful approach for non-invasive detection. This review compiles validated miRNAs implicated in the early stages of non-small-cell lung cancer (NSCLC), elucidating their roles in key oncogenic pathways such as epithelial-mesenchymal transition (EMT), <i>PI3K</i>/<i>AKT</i>/<i>mTOR</i>, and <i>JAK</i>-<i>STAT</i>, which regulate proliferation, apoptosis, and metastasis. Furthermore, we critically evaluate developed miRNA panels with a specific focus on advanced quantification and normalization strategies, including exogenous spike-in controls and data-driven methods like pairwise normalization, to enhance diagnostic accuracy. Consequently, we identify and rank the most viable miRNA candidates according to key analytical and clinical metrics, providing a clear roadmap for translating these biomarkers into effective panels for the timely detection of NSCLC.