Development and Validation of a Nine-Redox-Related Long Noncoding RNA Signature in Renal Clear Cell Carcinoma.

Development and Validation of a Nine-Redox-Related Long Noncoding RNA Signature in Renal Clear Cell Carcinoma.
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DOI:
10.1155/2020/6634247
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发表时间:
2020
影响因子:
--
通讯作者:
Wang SG
Wang SG
中科院分区:
生物学2区
文献类型:
--
作者:
Qi-Dong X;Yang X;Lu JL;Liu CQ;Sun JX;Li C;Wang SG

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氧化还原在肿瘤的发生、发展过程中起重要作用,可能受长非编码RNA(LncRNA)的调控。我们的目标是开发和验证一种新的氧化还原相关的基于LncRNA的肾透明细胞癌(CcRCC)预后标志。来自癌症基因组图谱(TCGA)的530名ccRCC患者被纳入本研究。所有样本按1 : 1比例随机分为训练组和试验组。然后,我们筛选了氧化还原相关的差异表达的lncRNA,并使用最小绝对收缩和选择操作(Lasso)和Cox回归从训练组构建了一个新的预后标志。接下来,为了验证签名的准确性,我们对训练组、测试组和所有样本进行了风险和生存分析,以及ROC曲线、诺模图和校准曲线的构建。最后,构建氧化还原基因-氧化还原相关的LncRNA相互作用网络,并进行基因集浓缩分析(GSEA)以了解氧化还原相关功能在高危人群和低危人群之间的状况。由AC025580.3、COLCA1、AC027601.2、DLEU2、AC004918.3、AP006621.2、AL031670.1、SPINT1-AS1和LAMA5-AS1组成的9个氧化还原相关的lncRNA特征与ccRCC患者的总体生存显著相关。签名被证明是有效的,因此,成功地组装了诺模图。此外,GSEA结果表明,在高危ccRCC患者中,两种主要的氧化还原相关功能增强。我们的发现有力地证明了9个氧化还原相关的lncRNA信号可以作为ccRCC的一个有效的预后指标。
Redox plays an essential role in the pathogeneses and progression of tumors, which could be regulated by long noncoding RNA (lncRNA). We aimed to develop and verify a novel redox-related lncRNA-based prognostic signature for clear cell renal cell carcinoma (ccRCC). A total of 530 ccRCC patients from The Cancer Genome Atlas (TCGA) were included in this study. All the samples were randomly split into training and test group at a 1 : 1 ratio. Then, we screened differentially expressed redox-related lncRNAs and constructed a novel prognostic signature from the training group using the least absolute shrinkage and selection operation (LASSO) and COX regression. Next, to verify the accuracy of the signature, we conducted risk and survival analysis, as well as the construction of ROC curve, nomogram, and calibration curves in the training group, test group, and all samples. Finally, the redox gene-redox-related lncRNA interaction network was constructed, and gene set enrichment analysis (GSEA) was performed to investigate the status of redox-related functions between high/low-risk groups. A nine-redox-related lncRNA signature consisted of AC025580.3, COLCA1, AC027601.2, DLEU2, AC004918.3, AP006621.2, AL031670.1, SPINT1-AS1, and LAMA5-AS1 was significantly associated with overall survival in ccRCC patients. The signature proved efficient, and thus, a nomogram was successfully assembled. In addition, the GSEA results demonstrated that two major redox-related functions were enhanced in the high-risk group ccRCC patients. Our findings robustly demonstrate that the nine-redox-related lncRNA signature could serve as an efficient prognostic indicator for ccRCC.
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