Identification of serum 5’tRF-Val as a promising non-invasive biomarker for early detection of esophageal cancer

Esophageal cancer (EC) is frequently detected at an advanced stage because of the lack of effective noninvasive screening tools, leading to poor prognosis. This study aimed to identify serum transfer RNA-derived small RNA (tsRNA) biomarkers for early detection of EC. Candidate tsRNAs were screened using the tsRFun database, and a quantitative real-time PCR (qRT‒PCR) method for serum 5'tRF-Val was subsequently established and validated. A total of 289 participants were enrolled, including 124 EC patients (71 with early-stage, 53 with advanced-stage disease), 56 individuals with benign lesions, 77 healthy subjects, and 32 postoperative EC patients. Detection performance was evaluated by receiver operating characteristic (ROC) curve analysis, and correlations with clinicopathological parameters were examined. 5'tRF-Val levels were significantly higher in the serum of EC patients than in that of healthy subjects. Its expression correlated positively with aggressive pathological features, including advanced TNM stage and the presence of metastasis. Notably, 5'tRF-Val demonstrated high detection accuracy for early-stage EC, with an AUC of 0.857. Importantly, it effectively distinguished early EC lesions from benign lesions (AUC = 0.824). Furthermore, longitudinal analysis revealed a significant decrease in 5'tRF-Val levels following radical surgery, suggesting its potential for monitoring treatment response. Serum 5'tRF-Val was identified in this study as a novel and promising noninvasive biomarker for the early detection of EC. Owing to its high detection accuracy, association with disease progression, and postoperative dynamic changes, 5'tRF-Val may help to fill the current gap in noninvasive detection of early EC, but this needs to be further verified in multicentre studies.