Serum 5'-tiRNA-iMet-CAT is a novel biomarker for the diagnosis and early postoperative assessment of hepatocellular carcinoma.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common digestive system malignancies and a leading cause of cancer-related mortality worldwide. Alpha-fetoprotein (AFP), although widely used, shows limited sensitivity in early HCC, leading to missed diagnoses. Novel molecular markers that complement existing biomarkers are urgently needed. tRNA-derived small RNAs (tsRNAs), a newly recognized class of noncoding RNAs generated from transfer RNAs, are abundant in cancer cells and body fluids and have emerging roles in tumourigenesis. This study aimed to identify dysregulated tsRNAs in HCC and evaluate their clinical value as biomarkers.

Methods: We performed high-throughput sequencing on 3 pairs of HCC tissues and their matched adjacent normal tissues to profile 5'-tiRNA-iMet-CAT, validating its serum levels by quantitative reverse transcription PCR (qRT-PCR). Molecular features and stability were confirmed by electrophoresis, sequencing, and freeze-thaw assays. We assessed clinical correlations, diagnostic potential, and predicted target genes via multiple databases with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.

Results: Serum 5'-tiRNA-iMet-CAT was significantly elevated in HCC patients versus healthy controls. Its high expression correlated with poor differentiation, larger tumour size, and advanced Barcelona Clinic Liver Cancer stage (all P < 0.05). Receiver operating characteristic analysis confirmed strong diagnostic performance, with levels markedly decreasing postoperatively (P < 0.0001).

Conclusion: Serum 5'-tiRNA-iMet-CAT is stable, specific, and clinically relevant. It may serve as a promising noninvasive biomarker for HCC diagnosis and evaluating short-term therapeutic response during the early postoperative phase.