Combinatorial analysis of miRNAs and tRNA fragments as potential biomarkers for cancer patients in liquid biopsies

Liquid biopsy has gained significant attention as a non-invasive method for cancer de-tection and monitoring. IsomiRs and tRNA-derived fragments (tRFs) are small non-coding RNAs that arise from non-canonical microRNA (miRNAs) processing and the cleavage of tRNAs, respectively. These small non-coding RNAs have emerged as promising cancer biomarkers, and their distinct expression patterns highlight the need for further exploration of their roles in cancer research. In this study, we investigated the differential expression profiles of miRNAs, isomiRs, and tRFs in plasma extracellular vesicles (EVs) from colorectal and prostate cancer patients compared to healthy controls. Subsequently, a combinatorial analysis using the CombiROC package was performed to identify a panel of biomarkers with optimal diagnostic accuracy. Our results demonstrate that a combination of miRNAs, isomiRs, and tRFs can effectively distinguish cancer patients from healthy controls, achieving accuracy and an area under the curve (AUC) of approximately 80%. These findings highlight the potential of a combinatorial approach to small RNA analysis in liquid biopsies for improved cancer diagnosis and management.