Advances in the role of extracellular vesicles in circulating microRNA biomarker discovery for lung cancer

Ayaz Belkozhayev^1,2*Minnatallah Al-Yozbaki³Yeldar Ashirbekov²Kantemir Satken²Arman Abaildayev^1,4Askar Yeleussizov⁵Nurlan Jainakbayev⁶Kamalidin Sharipov^2,7Cornelia M Wilson^8,9*

• ¹Department of Chemical and Biochemical Engineering, Geology and Oil-Gas Business Institute Named after K. Turyssov, Satbayev University, Almaty, Kazakhstan
• ²Structural and Functional Genomics Laboratory of M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, Almaty, Kazakhstan
• ³Department of Cancer and Genomics, School of Medical Sciences, College of Medicine and Health, University of Birmingham, Birmingham, United Kingdom
• ⁴Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty, Kazakhstan
• ⁵Kazakh Institute of Oncology and Radiology, Almaty, Kazakhstan
• ⁶Department of Public Health, Kazakh-Russian Medical University, Almaty, Kazakhstan
• ⁷Department of Biochemistry, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
• ⁸Canterbury Christ Church University, Life Sciences Industry Liaison Lab, School of Psychology and Life Sciences, Sandwich, United Kingdom
• ⁹Novel Global Community Educational Foundation, Hebersham, Australia

Lung cancer remains a leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis and the limited efficacy of current therapeutic approaches. Recent advancements highlight the potential of extracellular vesicles (EVs), particularly those carrying microRNA (miRNA) molecules, as promising non-invasive biomarkers for early detection, prognosis, and therapy monitoring. EVs are nanoscale vesicles secreted by tumour cells, capable of transporting various bioactive molecules including miRNAs while preserving their structural stability in circulation. These miRNAs mirror the molecular state of the tumour and often exhibit distinct expression signatures depending on cancer subtype and stage. Studies have shown that specific EV-associated miRNAs are significantly dysregulated in lung cancer patients and correlate with tumour progression, metastatic potential, and overall survival. Moreover, tracking dynamic changes in EV-miRNA profiles during treatment may provide predictive insights into responsiveness to immunotherapy and targeted therapy. This review emphasizes the diagnostic and prognostic utility of EV-derived miRNAs, highlighting their tumour specificity and stability in bodily fluids. In addition, we summarise key challenges such as the lack of standardisation, EV heterogeneity, and technical variability, while also outlining future directions including single-EV detection, multi-omics integration, AI-driven diagnostics, and therapeutic applications. By integrating these biomarkers into clinical workflows via liquid biopsy, it may become possible to detect lung cancer earlier and adapt therapeutic strategies more effectively ultimately improving patient outcomes and offering new directions in precision oncology.