Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer
Plasma tRNA Fragments Derived from 5′ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer
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DOI：
10.1016/j.omtn.2020.07.026
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发表时间：
2020-09-04
影响因子：
8.8
通讯作者：
Wang, Shui
中科院分区：
文献类型：
--
作者：
Wang, Jingyi;Ma, Ge;Wang, Shui
来自tRNA的小RNA引起了相当大的关注;然而，tRNA衍生片段（tRFs）和tRNA半体（tiRNAs）作为生物标志物在早期乳腺癌（EBC）中的作用尚未研究。该研究旨在探索是否可以在血浆中检测到tRFs和tiRNAs，以及它们是否可以作为诊断生物标志物。该研究分四个阶段进行。在筛选阶段通过高通量测序选择30个tRF和tiRNA，然后在训练、测试和外部验证阶段通过qRT-PCR进行评估。与正常对照组相比，EBC患者血浆中有6个tRFs（tRF-Glu-CTC-003、tRF-Gly-CCC-007、tRF-Gly-CCC-008、tRF-Leu-CAA-003、tRF-Ser-TGA-001和tRF-Ser-TGA-002）表达显著下调，均来源于tRNA的5'端。tRF-Glu-CTC-003低表达水平的HER 2 + EBC患者与更差的无病生存期和总生存期相关。在细胞上清液、从血浆分离的外来体和组织中进一步检查鉴定的tRF。总之，我们的研究从tRNA的5'端鉴定出6个tRFs作为EBC的新诊断生物标志物，为循环tRFs和EBC提供了额外的证据和更好的理解。
Small RNAs derived from tRNAs are attracting considerable attention; however, the effects of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) as biomarkers have not been investigated in early-stage breast cancer (EBC). The study aimed to explore whether tRFs and tiRNAs could be detected in plasma and whether they could serve as diagnostic biomarkers. The study was conducted in four phases. Thirty tRFs and tiRNAs were selected by high-throughput sequencing in screening phase and then assessed in training, testing, and external validation phases by qRT-PCR. Six tRFs (tRF-Glu-CTC-003, tRF-Gly-CCC-007, tRF-Gly-CCC-008, tRF-Leu-CAA-003, tRF-Ser-TGA-001, and tRF-Ser-TGA-002) were found significantly downregulated in plasma samples of patients with EBC compared with normal controls, and all were derived from 5' ends of tRNAs. Patients with HER2+ EBC with low expression levels of tRF-Glu-CTC-003 were related to worse disease-free survival and overall survival. The identified tRFs were further examined in cell supernatants, exosomes isolated from plasma, and tissues. In conclusion, our study identified six tRFs from the 5' ends of tRNAs as novel diagnostic biomarkers for EBC, providing additional evidence for, and a better understanding of, circulating tRFs and EBC.