Noncoding RNAs Serve as Diagnosis and Prognosis Biomarkers for Hepatocellular Carcinoma
Noncoding RNAs Serve as Diagnosis and Prognosis Biomarkers for Hepatocellular Carcinoma
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非编码 RNA 作为肝细胞癌的诊断和预后生物标志物
DOI：
10.1373/clinchem.2018.301150
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发表时间：
2019-07-01
影响因子：
9.3
通讯作者：
Lu, Zhi John
中科院分区：
文献类型：
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作者：
Tan, Chang;Cao, Jingyi;Lu, Zhi John
背景：目前迫切需要可靠的非侵入性肝癌诊断和预后生物标志物。我们不仅探索了微小RNA（miRNA），还探索了其他类型的非编码RNA（ncRNA）作为肝癌生物标志物的潜力。方法：收集了77名个体的外周血样本;其中，对57个无浆细胞RNA转录组和20个外泌体RNA转录组进行了分析。在一个独立的验证队列（60-150个样品）中，用逆转录（RT）-qPCR验证了显著上调的ncRNA和已发表的潜在HCC生物标志物。我们特别研究了1个ncRNA生物标志物RN 7SL 1及其S fragment.RESULTS的诊断和预后性能以及生物学功能：我们鉴定了某些循环ncRNA逃避RNA酶降解，可能是通过与RNA结合蛋白结合：899个ncRNA在HCC患者中高度上调。其中337个基因为片段化长非编码RNA，252个基因为核仁小RNA，134个基因为piwi相互作用RNA。筛选出48个候选基因，并通过RT-qPCR进行验证，其中16个ncRNA被证实在HCC中显著上调，包括RN 7SL 1、SNHG 1、ZFAS 1和LINC 01359。特别地，RN 7SL 1 S片段的丰度区分HCC样品与阴性对照（曲线下面积，0.87; 95%CI，0.817-0.920）。RN 7SL 1 S片段浓度较高的HCC患者生存率较低。此外，RN 7SL 1 S片段单独促进癌细胞增殖和克隆形成growth.CONCLUSIONS：我们的研究结果表明，各种ncRNA物种，不仅是miRNA，在血浆中的小RNA测序鉴定也能够作为非侵入性生物标志物。特别地，我们鉴定了sr-pRNA RN 7SL 1的结构域，其对于HCC诊断和预后具有可靠的临床表现。(C)2019年美国临床化学协会
BACKGROUND: Reliable noninvasive biomarkers for hepatocellular carcinoma (HCC) diagnosis and prognosis are urgently needed. We explored the potential of not only microRNAs (miRNAs) but other types of noncoding RNAs (ncRNAs) as HCC biomarkers.METHODS: Peripheral blood samples were collected from 77 individuals; among them, 57 plasma cell-free RNA transcriptomes and 20 exosomal RNA transcriptomes were profiled. Significantly upregulated ncRNAs and published potential HCC biomarkers were validated with reverse transcription (RT)-qPCR in an independent validation cohort (60-150 samples). We particularly investigated the diagnosis and prognosis performance and biological function for 1 ncRNA biomarker, RN7SL1, and its S fragment.RESULTS: We identified certain circulating ncRNAs escaping from RNase degradation, possibly through binding with RNA-binding proteins: 899 ncRNAs were highly upregulated in HCC patients. Among them, 337 genes were fragmented long noncoding RNAs, 252 genes were small nucleolar RNAs, and 134 genes were piwi-interacting RNAs. Forty-eight candidates were selected and validated with RT-qPCR, of which, 16 ncRNAs were verified to be significantly upregulated in HCC, including RN7SL1, SNHG1, ZFAS1, and LINC01359. Particularly, the abundance of RN7SL1 S fragment discriminated HCC samples from negative controls (area under the curve, 0.87; 95% CI, 0.817-0.920). HCC patients with higher concentrations of RN7SL1 S fragment had lower survival rates. Furthermore, RN7SL1 S fragment alone promoted cancer cell proliferation and clonogenic growth.CONCLUSIONS: Our results show that various ncRNA species, not only miRNAs, identified in the small RNA sequencing of plasma are also able to serve as noninvasive biomarkers. Particularly, we identified a domain of sr-pRNA RN7SL1 with reliable clinical performance for HCC diagnosis and prognosis. (C) 2019 American Association for Clinical Chemistry