Comparative Analysis of ncRNA Biomarkers in NSCLC: Exploring Diagnostic Potential and Addressing Gaps in Current Literature

This paper will provide a detailed systematic review of non-coding RNA (ncRNA) biomarkers, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in the early detection of non-small cell lung cancer (NSCLC).Based on the information obtained in more than 70 peerreviewed articles published in the period between 2005 and 2025, the diagnostic accuracy, reproducibility, and translational potential of the most important ncRNAs were critically compared.miRNA-21 was the most diagnostically effective of all biomarkers with pooled sensitivity and specificity of over 85 percent, and area under the curve (AUC) values of over 0.90 in multi-ethnic cohorts.Its strength, stability in plasma and serum and mechanistic significance in oncogenic pathways including PTEN/PI3K/AKT highlight its clinical feasibility.Other miRNAs such as miRNA-155, miRNA-20a, lncRNAs MALAT1 and HOTAIR, and circRNAs circRNA-100876, CDR1as and hsa-circ-0013958 had moderate to high AUCs (0.80-0.88) but were not consistently validated and standardized on a large scale.Relative evaluation showed that miRNAs are closest to clinical translation because of cost-effective and reproducible quantification by qRT-PCR, lncRNAs and circRNAs have long-term prospects of being integrated into multi-biomarker diagnostic panels.The discussion identifies significant barriers to translation, including biological variability, inconsistency in detection, and the absence of cross-population validation, but argues that combinatorial ncRNA panels, which are enabled by artificial intelligence and multi-omics integration, have the potential to enhance diagnostic accuracy to AUCs exceeding 0.95.In conclusion, miRNA-21 is the most promising ncRNA to be used in the nearest future, and multi-centre trials, standardisation of the analysis processes, and the use of diverse populations are the key factors that will convert the ncRNA research into clinically usable NSCLC diagnostics.