Application of cell-free RNA in liquid biopsy

Cell free RNA (cfRNA) based liquid biopsy is pushing noninvasive diagnostics forward, moving the field from a static view focused on genomics into a more dynamic space centered on functional transcriptomics. Circulating tumor DNA (ctDNA) mainly tells us about genetic alterations, but cfRNA provides a distinct informational dimension by capturing gene expression as it happens, along with splicing changes, non-coding regulation, and post-transcriptional modifications. This yields a more functional and comprehensive picture of disease biology. This review systematically examines the molecular features of cfRNA, contemporary analytical technologies, and clinical applications spanning early cancer detection, molecular subtyping, and prediction of pregnancy complications. Emerging dimensions including fragmentomics, epitranscriptomics, and microbial-derived cfRNA are also examined. Current challenges around standardization, sensitivity, and clinical validation are addressed. With advances in multi-omics integration and artificial intelligence, cfRNA has substantial potential to evolve from a supplementary biomarker into a core technology for early disease detection, longitudinal monitoring, and personalized treatment. The goal of this review is to delineate the current state of the field, identify key obstacles, and outline pathways through which cfRNA may achieve routine clinical implementation.