Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

Abstract

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.

Keywords

tsRNA / biomarker / hepatocarcinoma

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Acknowledgements

This study was supported by the Training Program of the Major Research Plan of the National Natural Science Foundation of China (No. 92049109), the National Natural Science Foundation of China (Nos. 32000549 and 82003024), the Natural Science Foundation of Jiangsu Province (No. BK2020041989), and the Natural Science Foundation of Nanjing University of Chinese Medicine (No. NZY82003024).

Compliance with ethics guidelines

Shoubin Zhan, Ping Yang, Shengkai Zhou, Ye Xu, Rui Xu, Gaoli Liang, Chenyu Zhang, Xi Chen, Liuqing Yang, Fangfang Jin, and Yanbo Wang declare that they have no conflict of interest. All the procedure of this study was approved by the Medical Ethics Committee of the Affiliated Drum Tower Hospital of Nanjing University Medical School and the First People’s Hospital of Lianyungang.

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Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-022-0920-7 and is accessible for authorized users.

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