Clinical value of blood circulating tumor RNA (ctRNA) in liquid biopsy of lung cancer: a narrative review

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Background and Objective: Lung cancer remains a major global health challenge, with substantial incidence rates and the highest cancer-related mortality. Liquid biopsy based on circulating tumor DNA (ctDNA) has been widely used in lung cancer diagnosis, monitoring, and treatment guidance. However, its sensitivity remains limited due to the low abundance of ctDNA in circulation. Circulating tumor RNA (ctRNA), released actively or passively by tumor cells and carrying tumor-specific alterations, offers a promising complementary biomarker in lung cancer liquid biopsy. This review summarizes current ctRNA research in lung cancer and highlights the potential of ctRNA approaches to improve diagnostic and monitoring performance. Methods: We performed a narrative review by systematically searching the PubMed and Google Scholar databases for identifying significant literatures related to clinical research for ctRNA in lung cancer. Key Content and Findings: This review summarizes the biological resources, including plasma, exosome, and platelet, and liquid biopsy techniques, such as quantitative polymerase chain reaction (qPCR), digital droplet PCR (ddPCR), nCounter, as well as next-generation sequencing (NGS) for ctRNA detection in lung cancer. In addition, we discuss the current clinical studies of ctRNA in diagnosis, prognosis, and monitoring, as well as its integration with ctDNA in liquid biopsy of lung cancer. Finally, we highlight the current limitations and further perspective of ctRNA in clinical applications. Conclusions: ctRNA represents a powerful and increasingly essential component of next-generation liquid biopsy. Its integration with ctDNA enhances molecular profiling and supports more precise diagnosis, dynamic disease monitoring, and adaptation of targeted therapies in lung cancer. Continued methodological advancements will further accelerate its clinical translation.

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