Non-coding RNAs predict recurrence-free survival of patients with hypoxic tumours.
Non-coding RNAs predict recurrence-free survival of patients with hypoxic tumours.
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DOI：
10.1038/s41598-017-18462-z
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发表时间：
2018-01-09
影响因子：
4.6
通讯作者：
Bennewith KL
中科院分区：
文献类型：
--
作者：
Martinez VD;Firmino NS;Marshall EA;Ng KW;Wadsworth BJ;Anderson C;Lam WL;Bennewith KL
低氧会增加肿瘤的侵袭性，降低患者的存活率。低氧肿瘤患者的不良预后表明，额外的因素调节了肿瘤对低氧的反应。Piwi相互作用RNA(PiRNAs)是一种小的非编码RNA，在基因组稳定性和基因表达的表观遗传调控中起着关键作用。我们报告了癌症类型特异性的piRNA签名在不同的患者中有所不同。然而，在肾癌患者中检测到显著同源的piRNA图谱，这种癌症的特征是由于常见的von Hippel-Lindau因子(VHL)突变或丢失而导致缺氧相关信号的结构性上调。通过研究来自七个器官的缺氧性和非缺氧性肿瘤的>；3000 piRNA转录本，我们发现了40个受缺氧调节的piRNA，并在低氧培养的细胞中验证了这一点。此外，在体外，这些受低氧调控的piRNAs的一部分受到VHL/HIF信号的调控。低氧调节的piRNA评分(PISCO)与低氧肿瘤，特别是I期肺腺癌的RFS差相关，这表明即使在早期肿瘤中，低氧调节的piRNA表达也可以预测肿瘤的复发，因此可能具有临床实用价值。
Hypoxia promotes tumour aggressiveness and reduces patient survival. A spectrum of poor outcome among patients with hypoxic tumours suggests that additional factors modulate how tumours respond to hypoxia. PIWI-interacting RNAs (piRNAs) are small non-coding RNAs with a pivotal role in genomic stability and epigenetic regulation of gene expression. We reported that cancer type-specific piRNA signatures vary among patients. However, remarkably homogenous piRNA profiles are detected across patients with renal cell carcinoma, a cancer characterized by constitutive upregulation of hypoxia-related signaling induced by common mutation or loss of von Hippel-Lindau factor (VHL). By investigating >3000 piRNA transcriptomes in hypoxic and non-hypoxic tumors from seven organs, we discovered 40 hypoxia-regulated piRNAs and validated this in cells cultured under hypoxia. Moreover, a subset of these hypoxia-regulated piRNAs are regulated by VHL/HIF signaling in vitro. A hypoxia-regulated piRNA-based score (PiSco) was associated with poor RFS for hypoxic tumours, particularly Stage I lung adenocarcinomas, suggesting that hypoxia-regulated piRNA expression can predict tumour recurrence even in early-stage tumours and thus may be of clinical utility.
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