Deciphering the contribution of 5’-tiRNA- Lys-CTT as an emerging early diagnostic biomarker for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide, with early detection critical for improving survival rates. Late-stage diagnosis contributes to dismal prognosis. Current surveillance relies on ultrasonography and serum alpha-fetoprotein (AFP), yet AFP exhibits limited sensitivity and specificity for early HCC. Emerging non-coding RNAs, particularly tRNA-derived small RNAs (tsRNAs), offer stable, detectable alternatives for liquid biopsy. Among these, 5′-tiRNA-Lys-CTT, a 5′-tRNA half derived from tRNA-Lys-CTT, has shown promise. This commentary explores the potential of 5′-tiRNA-Lys-CTT, a tRNA-derived small RNA (tsRNA), as an emerging biomarker for early HCC detection. It integrates biology, diagnostic performance along with recent advancements in tsRNA research for Hepatocellular carcinoma (HCC), and discusses potential clinical applications for enhanced early detection and personalized therapy. Ultimately, 5′-tiRNA-Lys-CTT represents a promising avenue for liquid biopsy-based screening, potentially revolutionizing HCC management.