Eight-lncRNA signature of cervical cancer were identified by integrating DNA methylation, copy number variation and transcriptome data.
Eight-lncRNA signature of cervical cancer were identified by integrating DNA methylation, copy number variation and transcriptome data.
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通过整合DNA甲基化、拷贝数变异和转录组数据，鉴定出宫颈癌的八个lncRNA特征
DOI：
10.1186/s12967-021-02705-9
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发表时间：
2021-02-08
影响因子：
7.4
通讯作者：
Hang J
中科院分区：
文献类型：
--
作者：
Zhong Q;Lu M;Yuan W;Cui Y;Ouyang H;Fan Y;Wang Z;Wu C;Qiao J;Hang J
拷贝数变化（CNV）表明恶性肿瘤的遗传变化。长期非编码RNA（LNCRNA）的异常表达是由基因组和表观遗传异常引起的，在宫颈癌的肿瘤发生中起着驱动作用。然而，LNCRNA相关的CNV在宫颈癌中的作用仍然在很大程度上不清楚。
从292个宫颈癌标本中收集了信使RNA（mRNA），DNA甲基化和DNA拷贝数的数据。通过多词综合分析确定了与宫颈癌的预后相关亚型，并鉴定出具有亚型特异性表达的蛋白质编码基因（PCGS）和LNCRNA。分析了亚型特异性LNCRNA的CNV模式，以鉴定亚型特异性LNCRNA。至少绝对收缩和选择操作员（Lasso）建立了基于LNCRNA的预后风险模型。
多词集成分析确定了三个分子亚型，其中包括617个差异表达的LNCRNA和1395个差异表达的PCG。发现617个LNCRNA与疾病相关的LNCRNA相交。功能富集表明，有617个LNCRNA主要参与肿瘤代谢，免疫力和其他途径，例如p53和CAMP信号通路，这些途径与宫颈癌的发展密切相关。最后，根据CNV模式与差异表达分析一致，我们建立了一个基于LNCRNA的签名，包括8个LNCRNA，即RUSC1-AS1，LINC01990，LINC01411，LINC01411，LINC02099，LINC02099，H19，H19，H19，H19，H19，LINC00452，adpgk-as1，adpgk-as1，c1qtnf1-as1-as1。 8个LNCRNA的相互作用显示宫颈癌患者的预后明显较差，这也已在独立的数据集中进行了验证。
我们的研究扩大了CNV的网络，并提高了对宫颈癌中LNCRNA的调节网络的理解，为宫颈癌患者的预后管理提供了新的生物标志物。
BackgroundCopy number variation (CNV) suggests genetic changes in malignant tumors. Abnormal expressions of long non-coding RNAs (lncRNAs) resulted from genomic and epigenetic abnormalities play a driving role in tumorigenesis of cervical cancer. However, the role of lncRNAs-related CNV in cervical cancer remained largely unclear.MethodsThe data of messenger RNAs (mRNAs), DNA methylation, and DNA copy number were collected from 292 cervical cancer specimens. The prognosis-related subtypes of cervical cancer were determined by multi-omics integration analysis, and protein-coding genes (PCGs) and lncRNAs with subtype-specific expressions were identified. The CNV pattern of the subtype-specific lncRNAs was analyzed to identify the subtype-specific lncRNAs. A prognostic risk model based on lncRNAs was established by least absolute shrinkage and selection operator (LASSO).ResultsMulti-omics integration analysis identified three molecular subtypes incorporating 617 differentially expressed lncRNAs and 1395 differentially expressed PCGs. The 617 lncRNAs were found to intersect with disease-related lncRNAs. Functional enrichment showed that 617 lncRNAs were mainly involved in tumor metabolism, immunity and other pathways, such as p53 and cAMP signaling pathways, which are closely related to the development of cervical cancer. Finally, according to CNV pattern consistent with differential expression analysis, we established a lncRNAs-based signature consisted of 8 lncRNAs, namely, RUSC1-AS1, LINC01990, LINC01411, LINC02099, H19, LINC00452, ADPGK-AS1, C1QTNF1-AS1. The interaction of the 8 lncRNAs showed a significantly poor prognosis of cervical cancer patients, which has also been verified in an independent dataset.ConclusionOur study expanded the network of CNVs and improved the understanding on the regulatory network of lncRNAs in cervical cancer, providing novel biomarkers for the prognosis management of cervical cancer patients.
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影响因子：
3
作者：
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通讯作者：
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影响因子：
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影响因子：
3.7
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影响因子：
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作者：
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DOI：
10.1080/21691401.2019.1577883
发表时间：
2019-01-01
影响因子：
5.8
作者：
Gao, Fangyuan;Feng, Jing;Yang, Jun
通讯作者：
Yang, Jun