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On-line Access: 2021-08-20

Received: 2020-08-30

Revision Accepted: 2021-01-25

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Jianguang QIU

https://orcid.org/0000-0002-3517-4110

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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.8 P.664-681

http://doi.org/10.1631/jzus.B2000494


Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer


Author(s):  Wenwen ZHONG, Dejuan WANG, Bing YAO, Xiaoxia CHEN, Zhongyang WANG, Hu QU, Bo MA, Lei YE, Jianguang QIU

Affiliation(s):  Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China; more

Corresponding email(s):   qiujg@mail.sysu.edu.cn

Key Words:  Bladder cancer, Copy number variation (CNV), Long non-coding RNA (lncRNA), Prognosis


Wenwen ZHONG, Dejuan WANG, Bing YAO, Xiaoxia CHEN, Zhongyang WANG, Hu QU, Bo MA, Lei YE, Jianguang QIU. Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer[J]. Journal of Zhejiang University Science B, 2021, 22(8): 664-681.

@article{title="Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer",
author="Wenwen ZHONG, Dejuan WANG, Bing YAO, Xiaoxia CHEN, Zhongyang WANG, Hu QU, Bo MA, Lei YE, Jianguang QIU",
journal="Journal of Zhejiang University Science B",
volume="22",
number="8",
pages="664-681",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000494"
}

%0 Journal Article
%T Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer
%A Wenwen ZHONG
%A Dejuan WANG
%A Bing YAO
%A Xiaoxia CHEN
%A Zhongyang WANG
%A Hu QU
%A Bo MA
%A Lei YE
%A Jianguang QIU
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 8
%P 664-681
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000494

TY - JOUR
T1 - Integrative analysis of prognostic long non-coding RNAs with copy number variation in bladder cancer
A1 - Wenwen ZHONG
A1 - Dejuan WANG
A1 - Bing YAO
A1 - Xiaoxia CHEN
A1 - Zhongyang WANG
A1 - Hu QU
A1 - Bo MA
A1 - Lei YE
A1 - Jianguang QIU
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 8
SP - 664
EP - 681
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000494


Abstract: 
Copy number variations (CNVs), which can affect the role of long non-coding RNAs (lncRNAs), are important genetic changes seen in some malignant tumors. We analyzed lncRNAs with CNV to explore the relationship between lncRNAs and prognosis in bladder cancer (BLCA). Messenger RNA (mRNA) expression levels, DNA methylation, and DNA copy number data of 408 BLCA patients were subjected to integrative bioinformatics analysis. Cluster analysis was performed to obtain different subtypes and differently expressed lncRNAs and coding genes. Weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression gene and lncRNA modules. CNV-associated lncRNA data and their influence on cancer prognosis were assessed with Kaplan-Meier survival curve. Multi-omics integration analysis revealed five prognostic lncRNAs with CNV, namely NR2F1-AS1, LINC01138, THUMPD3-AS1, LOC101928489, and TMEM147-AS1, and a risk-score signature related to overall survival in BLCA was identified. Moreover, validated results in another independent Gene Expression Omnibus (GEO) dataset, GSE31684, were consistent with these results. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the mitogen-activated protein kinase (MAPK) signaling pathway, focal adhesion pathway, and Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway were enriched in a high-risk score pattern, suggesting that imbalance in these pathways is closely related to tumor development. We revealed the prognosis-related lncRNAs by analyzing the expression profiles of lncRNAs and CNVs, which can be used as prognostic biomarkers for BLCA.

长非编码RNA和拷贝数变异关联分析鉴定和验证膀胱癌lncRNA预后标志物

目的:探讨伴有拷贝数变异(copy number variation (CNV))的长非编码RNA(long non-coding RNAs (LncRNAs))在膀胱癌中的作用。
创新点:鉴定与膀胱癌生存预后密切相关的伴有CNV的lncRNAs,构建风险评分模型。
方法:对The Cancer Genome Atlas(TCGA)数据库中408例膀胱癌患者的mRNA、DNA甲基化和DNA拷贝数数据进行综合生物信息学分析,筛选获得不同的亚型、差异表达lncRNAs和编码基因,采用加权基因共表达网络分析(weighted gene co-expression network analysis(WGCNA))方法鉴定共表达基因和lncRNA模块。使用Kaplan-Meier生存曲线评估CNV相关的lncRNAs对膀胱癌预后的影响,并用GSE31684数据集进行验证。
结论:多组学整合分析显示与CNV相关的NR2F1-AS1LINC01138THUMPD3-AS1LOC101928489TMEM147-AS1是膀胱癌中的预后因子,并利用这些lncRNAs构建与膀胱癌的总生存预后有关的风险评估模型,且在GSE31684数据集中得到验证。这些lncRNAs可作为膀胱癌的预后生物标志物。

关键词:膀胱癌;拷贝数变异;长非编码RNA;预后

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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