Prediction of bladder cancer outcome by identifying and validating a mutation-derived genomic instability-associated long noncoding RNA (lncRNA) signature

Hao Wu; Zi-Yi Zhang; Ze Zhang; Xin-Ying Xiao; Sheng-Lin Gao; Chao Lu; Li Zuo; Li-Feng Zhang

doi:10.1080/21655979.2021.1924555

Prediction of bladder cancer outcome by identifying and validating a mutation-derived genomic instability-associated long noncoding RNA (lncRNA) signature

Bioengineered. 2021 Dec;12(1):1725-1738. doi: 10.1080/21655979.2021.1924555.

Authors

Hao Wu^{1

2}, Zi-Yi Zhang^{1

2}, Ze Zhang^{1

2}, Xin-Ying Xiao³, Sheng-Lin Gao¹, Chao Lu¹, Li Zuo¹, Li-Feng Zhang¹

Affiliations

¹ Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
² Graduate School, Dalian Medical University, Dalian, China.
³ Medical College, Shantou University, Shantou, China.

Abstract

Bladder cancer is one of the most common malignant tumors worldwide. Accordingly, its incidence and mortality are high. One of the characteristics of cancer is genomic instability. New studies suggest that long non-coding RNAs (lncRNAs) play an important role in maintaining genomic instability. This study aimed to identify a genomic instability-associated lncRNA signature to predict the outcome of patients with bladder cancer. We downloaded data for bladder cancer patients from The Cancer Genome Atlas database to obtain lncRNA expression profiles as well as somatic mutation profiles. Using the lncRNA computational framework, a genomic instability-related lncRNA signature (GIlncSig) was established and the prognostic value of this signature was assessed and validated. A five-lncRNA signature based on genomic instability (CFAP58-DT, MIR100HG, LINC02446, AC078880.3, and LINC01833) was obtained from 58 differentially expressed lncRNAs. Patients were divided into high-risk and low-risk groups, with the high-risk group having a substantially worse prognosis than the low-risk group. Univariate and multivariate Cox analyses indicated that GIlncSig may be an independent prognostic factor; this finding was subsequently validated. In addition, enrichment analysis indicated that GIlncSig is associated with genomic instability in bladder cancer. GIlncSig has a predictive value for the prognosis of bladder cancer patients and provides guidance for the clinical treatment of these patients.

Keywords: Genome instability; bladder cancer; geo; long non-coding rnas; tcga.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Female
Gene Expression Profiling*
Gene Expression Regulation, Neoplastic / drug effects
Gene Regulatory Networks / drug effects
Genomic Instability*
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Mutation / genetics*
Prognosis
Proportional Hazards Models
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
ROC Curve
Reproducibility of Results
Treatment Outcome
Urinary Bladder Neoplasms / drug therapy
Urinary Bladder Neoplasms / genetics*
Urinary Bladder Neoplasms / pathology

Substances

Antineoplastic Agents
RNA, Long Noncoding

Grants and funding

Young Talent Development Plan of Changzhou Health Commission (No. CZQM2020065), Young Scientists Foundation of Changzhou No.2 People’s Hospital (2019K008), Changzhou Sci & Tech program (CJ20190100), the Second Hospital of Changzhou Discipline Funding (YJXK202013), Changzhou Innovation Team Funding (XK201803), Changzhou Top Talent Project (RC201620).