A novel diagnostic signature of circulating tsRNAs and miRNAs in esophageal squamous cell carcinoma detected with a microfluidic platform

Small non-coding RNAs (sncRNAs) consisting of tRNA-derived small RNAs (tsRNAs) and miRNAs can be released by cancer cells and detected in blood, offering great potential for diagnosis of malignant tumors such as squamous cell carcinoma of the esophagus (ESCC). One of the major challenges for the clinical application of blood-based sncRNAs biomarkers is the difficulty of detection because of their small sncRNA size and low abundance. The deferentially expressed tsRNAs and miRNAs in plasma were studied with high-throughput sequencing and polymerase chain reaction in ESCC cohorts. A novel signature containing tRF-55:74-chrM.Phe-GAA, tRF-56:75-Ala-CGC-1-M4 and miR-4488 was identified with diagnostic potential. The signature was further confirmed by an attomolar-level ultrasensitive and rapid microfluidic biochip, which can achieve a multiplex, simple and low-cost detection. Our results indicated that a combination of tsRNAs and miRNAs has high diagnostic efficiency and tremendous potential to act as specific biomarkers through a reliable, highly sensitive, fast, and economic microfluidic biochip for ESCC diagnosis.