The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer.
The significance of PIWI family expression in human lung embryogenesis and non-small cell lung cancer.
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DOI：
10.18632/oncotarget.3003
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发表时间：
2015-10-13
期刊：
影响因子：
--
通讯作者：
Monzo M
中科院分区：
文献类型：
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作者：
Navarro A;Tejero R;Viñolas N;Cordeiro A;Marrades RM;Fuster D;Caritg O;Moises J;Muñoz C;Molins L;Ramirez J;Monzo M
Piwi相互作用RNA（与PIWI蛋白结合的小RNA）的表达直到最近才被认为仅限于生殖干细胞。我们研究了PIWI基因在人肺胚胎发生过程中的表达，以及在配对的肿瘤和正常组织中的表达，这些组织是从71例切除的非小细胞肺癌患者中前瞻性收集的。mRNA表达分析表明，PIWIL 1在7周胚胎中高表达，在随后的发育周中下调。PIWIL 1在11个肿瘤样品中表达，但在正常组织样品中没有表达。这些结果通过免疫组织化学验证，在PIWIL 1阳性样品中显示微弱的细胞质反应性。有趣的是，表达PIWIL 1的患者比不表达PIWIL 1的患者具有更短的复发时间（TTR）（p = 0.006）和总生存期（OS）（p = 0.0076）。与正常组织相比，PIWIL 2和4在肿瘤组织中下调（p < 0.001），并且具有较低PIWIL 4水平的患者具有较短的TTR（p = 0.048）和OS（p = 0.033）。在多变量分析中，PIWIL 1表达成为独立的预后指标。使用5-Aza-dC处理和亚硫酸氢盐测序，我们观察到PIWIL 1的表达可以部分地通过甲基化来调节。最后，一项计算机模拟研究确定了与PIWIL 1表达相关的干细胞表达特征。
The expression of Piwi-interacting RNAs, small RNAs that bind to PIWI proteins, was until recently believed to be limited to germinal stem cells. We have studied the expression of PIWI genes during human lung embryogenesis and in paired tumor and normal tissue prospectively collected from 71 resected non-small-cell lung cancer patients. The mRNA expression analysis showed that PIWIL1 was highly expressed in 7-week embryos and downregulated during the subsequent weeks of development. PIWIL1 was expressed in 11 of the tumor samples but in none of the normal tissue samples. These results were validated by immunohistochemistry, showing faint cytoplasmic reactivity in the PIWIL1-positive samples. Interestingly, the patients expressing PIWIL1 had a shorter time to relapse (TTR) (p = 0.006) and overall survival (OS) (p = 0.0076) than those without PIWIL1 expression. PIWIL2 and 4 were downregulated in tumor tissue in comparison to the normal tissue (p < 0.001) and the patients with lower levels of PIWIL4 had shorter TTR (p = 0.048) and OS (p = 0.033). In the multivariate analysis, PIWIL1 expression emerged as an independent prognostic marker. Using 5-Aza-dC treatment and bisulfite sequencing, we observed that PIWIL1 expression could be regulated in part by methylation. Finally, an in silico study identified a stem-cell expression signature associated with PIWIL1 expression.