ABSTRACT As a promising candidate in liquid biopsy, tRNA‐derived small RNAs (tsRNAs) have been implicated as potential diagnostic biomarkers for cancer; however, the diagnostic potential of serum cell‐free tsRNAs in non‐small cell lung cancer (NSCLC) remains unexplored. This study aimed to develop a combinatorial model based on serum cell‐free tsRNA signatures and evaluated its diagnostic performance for NSCLC detection. Through systematic screening from the tsRFun database, we identified 32 NSCLC‐related differentially expressed tsRNAs, whose predicted target genes were significantly enriched in the MAPK pathway. Four MAPK pathway‐associated tsRNAs were selected for further validation due to their robust discriminatory power in distinguishing NSCLC patients from healthy control. Subsequent validation via quantitative RT‐PCR confirmed significantly elevated serum levels of tsRNA‐Thr‐5‐0039, tsRNA‐Thr‐5‐0044, and tsRNA‐Cys‐5‐0011 in NSCLC patients compared to healthy controls. The final combinatorial diagnostic model incorporating these three tsRNAs achieved an AUC of 0.83 (95% CI: 0.70–0.95), with 71.8% accuracy, 52.6% sensitivity, and 90.0% specificity. The three‐tsRNA model outperformed individual tsRNAs in diagnostic efficiency. In conclusion, these findings highlight the diagnostic potential of circulating tsRNA signatures as a minimally invasive liquid biopsy approach, offering new perspectives for early diagnosis of NSCLC.
Hu et al. (Fri,) studied this question.