通过整合 DNA 甲基化、拷贝数变异和转录组数据，鉴定了宫颈癌的 8 个长链非编码 RNA 特征。

Eight-lncRNA signature of cervical cancer were identified by integrating DNA methylation, copy number variation and transcriptome data.

机构信息

Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Peking University, HaiDian District, No. 38 XueYuan Road, Beijing, 100191, China.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, HaiDian District, No. 49 North HuaYuan Road, Beijing, 100191, China.

出版信息

J Transl Med. 2021 Feb 8;19(1):58. doi: 10.1186/s12967-021-02705-9.

DOI:10.1186/s12967-021-02705-9

PMID:33557879

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8045209/

Abstract

BACKGROUND

Copy 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.

METHODS

The 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).

RESULTS

Multi-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.

CONCLUSION

Our 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.

摘要

背景

拷贝数变异（CNV）提示恶性肿瘤中的遗传变化。由于基因组和表观遗传异常导致的长非编码 RNA（lncRNA）异常表达在宫颈癌的发生中起驱动作用。然而，lncRNA 相关 CNV 在宫颈癌中的作用在很大程度上仍不清楚。

方法

从 292 例宫颈癌标本中收集信使 RNA（mRNA）、DNA 甲基化和 DNA 拷贝数数据。通过多组学整合分析确定宫颈癌的预后相关亚型，并鉴定具有亚型特异性表达的蛋白编码基因（PCG）和 lncRNA。分析亚型特异性 lncRNA 的 CNV 模式，以鉴定亚型特异性 lncRNA。通过最小绝对收缩和选择算子（LASSO）建立基于 lncRNA 的预后风险模型。

结果

多组学整合分析确定了包含 617 个差异表达 lncRNA 和 1395 个差异表达 PCG 的三个分子亚型。发现 617 个 lncRNA 与疾病相关 lncRNA 重叠。功能富集表明，617 个 lncRNA 主要参与肿瘤代谢、免疫等途径，如 p53 和 cAMP 信号通路，这些途径与宫颈癌的发生发展密切相关。最后，根据与差异表达分析一致的 CNV 模式，我们建立了一个由 8 个 lncRNA 组成的基于 lncRNA 的特征，即 RUSC1-AS1、LINC01990、LINC01411、LINC02099、H19、LINC00452、ADPGK-AS1、C1QTNF1-AS1。这 8 个 lncRNA 的相互作用显示出宫颈癌患者预后明显较差，这在独立数据集也得到了验证。