Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis
Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis
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DOI：
10.1007/s11684-022-0920-7
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发表时间：
2022-04-13
影响因子：
8.1
通讯作者：
Wang, Yanbo
中科院分区：
文献类型：
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作者：
Zhan, Shoubin;Yang, Ping;Wang, Yanbo
肝细胞癌（Hepatocellular carcinoma，HCC）是由B/C型肝炎病毒感染引起的，占肝癌的大多数。需要生物标志物来促进HCC的早期检测，HCC通常诊断得太晚，无法进行有效治疗。tRNA衍生的小RNA（tsRNA）在肿瘤发生中起重要作用，并且在循环中稳定。然而，循环tsRNA的诊断价值和生物学功能，特别是对于HCC，仍然是未知的。在这项研究中，我们首先利用RNA测序，然后定量逆转录PCR分析肝癌血清中的tsRNA签名。我们鉴定了tRF-Gln-TTG-006，其在HCC血清中显著上调（训练群组：24名HCC患者对比24名健康对照）。在验证阶段，我们发现tRF-Gln-TTG-006特征可以区分HCC病例与健康受试者，即使在早期阶段也具有高灵敏度（80.4%）和特异性（79.4%）（阶段I：灵敏度，79.0%;特异性，74.8%;来自两个队列的155名健康对照对153名HCC患者）。体外研究表明，循环tRF-Gln-TTG-006可从肿瘤细胞中释放，生物信息学分析预测了其生物学功能，集落形成和凋亡实验验证了其生物学功能。总之，我们的研究表明，血清中的tsRNA签名可能作为一种新的生物标志物的肝癌。
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.