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一个与自噬相关的长非编码 RNA 标志物用于脑胶质瘤。

An autophagy-related long non-coding RNA signature for glioma.

机构信息

Department of Neurosurgery Affiliated Tumor Hospital of Guangxi Medical University Nanning China.

Department of Ultrasound Affiliated Tumor Hospital of Guangxi Medical University Nanning China.

出版信息

FEBS Open Bio. 2019 Mar 5;9(4):653-667. doi: 10.1002/2211-5463.12601. eCollection 2019 Apr.

Abstract

Glioma is one of the most common types of malignant primary central nervous system tumor, and prognosis for this disease is poor. As autophagic drugs have been reported to induce glioma cell death, we investigated the potential prognostic role of autophagy-associated long non-coding RNA (lncRNA) in glioma patients. In this study, we obtained 879 lncRNAs and 216 autophagy genes from the Chinese Glioma Genome Atlas microarray, and found that 402 lncRNAs are correlated with the autophagy genes. Subsequently, 10 autophagy-associated lncRNAs with prognostic value (, , , , , , , , -AS1 and ) were identified in glioma patients using multivariate Cox regression analyses. A prognostic signature was then established based on these prognostic lncRNAs, dividing patients into low-risk and high-risk groups. The overall survival time was shorter in the high-risk group than that in the low-risk group [hazard ratio (HR) = 5.307, 95% CI: 4.195-8.305;  < 0.0001]. Gene set enrichment analysis revealed that the gene sets were significantly enriched in cancer-related pathways, including interleukin (IL) 6/Janus kinase/signal transducer and activator of transcription (STAT) 3 signaling, tumor necrosis factor α signaling via nuclear factor κB, IL2/STAT5 signaling, the p53 pathway and the KRAS signaling pathway. The Cancer Genome Atlas dataset was used to validate that high-risk patients have worse survival outcomes than low-risk patients (HR = 1.544, 95% CI: 1.110-2.231;  = 0.031). In summary, our signature of 10 autophagy-related lncRNAs has prognostic potential for glioma, and these autophagy-related lncRNAs may play a key role in glioma biology.

摘要

神经胶质瘤是最常见的原发性中枢神经系统恶性肿瘤之一,其预后较差。由于自噬药物已被报道可诱导神经胶质瘤细胞死亡,因此我们研究了自噬相关长链非编码 RNA(lncRNA)在神经胶质瘤患者中的潜在预后作用。在这项研究中,我们从中国神经胶质瘤基因组图谱微阵列中获得了 879 个 lncRNA 和 216 个自噬基因,并发现 402 个 lncRNA 与自噬基因相关。随后,我们使用多变量 Cox 回归分析在神经胶质瘤患者中鉴定出 10 个具有预后价值的自噬相关 lncRNA(,,,,,,,,-AS1 和)。然后基于这些预后 lncRNA 建立了一个预后标志,将患者分为低风险和高风险组。与低风险组相比,高风险组的总生存时间更短[风险比(HR)=5.307,95%置信区间:4.195-8.305;<0.0001]。基因集富集分析显示,基因集在癌症相关途径中显著富集,包括白细胞介素(IL)6/Janus 激酶/信号转导和转录激活因子(STAT)3 信号、核因子κB 介导的肿瘤坏死因子α信号、IL2/STAT5 信号、p53 途径和 KRAS 信号通路。使用癌症基因组图谱数据集验证了高风险患者的生存结果比低风险患者差(HR=1.544,95%置信区间:1.110-2.231;=0.031)。总之,我们的 10 个自噬相关 lncRNA 特征具有神经胶质瘤的预后潜力,这些自噬相关 lncRNA 可能在神经胶质瘤生物学中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/653b/6443865/9fc2bef39361/FEB4-9-653-g001.jpg

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