Hepatocellular carcinoma(HCC),which makes up the majority of liver cancer,is induced by the infection of hepatitis B/C virus.Biomarkers are needed to facilitate the early detection of HCC,which is often diagnosed too late for effective therapy.The tRNA-derived small RNAs(tsRNAs)play vital roles in tumorigenesis and are stable in circulation.However,the diagnostic values and biological functions of circulating tsRNAs,especially for HCC,are still unknown.In this study,we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum.We identified tRF-Gln-TTG-006,which was remarkably upregulated in HCC serum(training cohort:24 HCC patients vs.24 healthy controls).In the validation stage,we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity(80.4％)and specificity(79.4％)even in the early stage(Stage Ⅰ:sensitivity,79.0％;specificity,74.8％;155 healthy controls vs.153 HCC patients from two cohorts).Moreover,in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells,and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays.In summary,our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

Shoubin Zhan;Ping Yang;Shengkai Zhou;Ye Xu;Rui Xu;Gaoli Liang;Chenyu Zhang;Xi Chen;Liuqing Yang;Fangfang Jin;Yanbo Wang

Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy,State Key Laboratory of Pharmaceutical Biotechnology and Department of Physiology,Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology,NJU Advanced Institute of Life Sciences(NAILS),School of Life Sciences,Nanjing University,Nanjing 210023,China;Department of Clinical Laboratory,The Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210023,China;Department of Infectious Diseases,The First People's Hospital of Lianyungang,The First Affiliated Hospital of Kangda College of Nanjing Medical University,Lianyungang 222000,China;School of Medicine&Holistic Integrative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China

医学前沿

[1]Shoubin Zhan;Ping Yang;Shengkai Zhou;Ye Xu;Rui Xu;Gaoli Liang;Chenyu Zhang;Xi Chen;Liuqing Yang;Fangfang Jin;Yanbo Wang-.Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis)[J].医学前沿,2022(02):216-226

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