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

• Published in: Journal of Zhejiang University. B. Science Vol. 22; no. 8; pp. 664 - 681
• Main Authors: Zhong, Wenwen, Wang, Dejuan, Yao, Bing, Chen, Xiaoxia, Wang, Zhongyang, Qu, Hu, Ma, Bo, Ye, Lei, Qiu, Jianguang
• Format: Journal Article
• Language: English
• Published: Hangzhou Zhejiang University Press 15.08.2021; Springer Nature B.V; Department of Urology,the Sixth Affiliated Hospital of Sun Yat-sen University,Guangzhou 510655,China%Department of Medical Record Management Section,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China
• Subjects: Bioinformatics; Biomarkers; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Bladder; Bladder cancer; Cancer; Cluster Analysis; Computational Biology; Copy number; Deoxyribonucleic acid; DNA; DNA Copy Number Variations; DNA methylation; Encyclopedias; Gene expression; Genes; Genomes; Humans; Janus kinase; Kaplan-Meier Estimate; Kinases; MAP kinase; Medical prognosis; Network analysis; Non-coding RNA; Prognosis; Protein kinase; Research Article; RNA, Long Noncoding - genetics; Signal transduction; Signaling; Survival; Transcription factors; Transducers; Tumors; Urinary Bladder Neoplasms - genetics; 拷贝数变异; Prognosis; Long non-coding RNA (lncRNA); 长非编码RNA; 预后; Bladder cancer; 膀胱癌; Copy number variation (CNV)
• ISSN: 1673-1581; 1862-1783
• DOI: 10.1631/jzus.B2000494

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.