Transfer RNA-derived small RNAs transform the landscape of liquid biopsy

A new review highlights the transformative potential of transfer RNA-derived small RNAs (tsRNAs) in the field of liquid biopsy, emphasizing their role as promising biomarkers for a wide range of diseases, particularly cancers. These non-coding RNA fragments, originating from mature or precursor tRNAs, are detectable in diverse body fluids—including blood plasma, saliva, urine, semen, and cerebrospinal fluid—and exhibit remarkable stability, even in challenging biological environments.

The article presents tsRNAs as a rising star in precision medicine, with significant diagnostic and prognostic value. Found in both plasma and serum, tsRNAs offer disease-specific expression patterns and correlate with key clinical features such as tumor stage, metastasis, and patient survival. In breast cancer, certain circulating tsRNAs are associated with improved prognostic accuracy compared to traditional markers, while in lung cancer, tsRNA signatures have helped differentiate between early and advanced stages. tsRNAs have also shown promise in gastrointestinal, ovarian, pancreatic, renal, and bladder cancers, as well as in conditions like nonalcoholic fatty liver disease, systemic lupus erythematosus, infertility, and neurodegenerative disorders.

A notable advantage of tsRNAs is their presence across multiple biofluids, enabling non-invasive sampling that is more accessible and less risky than tissue biopsies. This versatility opens up opportunities for early detection, disease monitoring, and treatment stratification. Importantly, tsRNAs demonstrate unique expression profiles distinct from similar small RNA classes like miRNAs, reinforcing their biological relevance and clinical utility.

The article also discusses challenges such as inconsistent nomenclature, variation in sample preparation, and the need for optimized detection platforms like PANDORA-seq. It calls for standardized analytical frameworks to enable consistent cross-study comparisons and emphasizes the importance of accounting for age-related and tissue-specific variation in tsRNA expression.