Identification of serum tsRNA-Thr-5-0015 and combined with AFP and PIVKA-II as novel biomarkers for hepatocellular carcinoma

Accumulating evidence has shown that tRNA-derived small RNAs (tsRNAs) play crucial roles in malignant tumor development. However, whether serum tsRNAs can act as potential biological markers for hepatocellular carcinoma (HCC) are still largely unknown. In the current study, a novel tsRNA, namely tsRNA-Thr-5-0015, was prominently elevated in the sera of HCC patients than that of hepatitis cases and healthy check-ups, and it was related with TNM stage and lymphatic metastasis of HCC patients. Moreover, methodological evaluation confirmed that tsRNA-Thr-5-0015 had excellent stability, precision, accuracy and linear range. Additionally, the combined detection of serum tsRNA-Thr-5-0015 with AFP as well as PIVKA-II improved the diagnostic sensitivity for HCC. Furthermore, dynamic monitoring found that the serum tsRNA-Thr-5-0015 was drastically decreased in the postoperative HCC patients. Besides, Kaplan–Meier analysis displayed that patients with high level of serum tsRNA-Thr-5-0015 had shorter overall survival than that of the low level ones. In addition, bioinformatic prediction unveiled that the downstream targets of tsRNA-Thr-5-0015 were enriched in several signaling pathways, such as MAPK, PI3K-Akt, etc. In summary, tsRNA-Thr-5-0015 may be a promising biomarker for HCC diagnosis, therapeutic effect assessment and prognosis judgement. Especially, the combination with serum tsRNA-Thr-5-0015, AFP and PIVKA-II can enhance the diagnostic efficiency for HCC.