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

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.

ABSTRACT

KEYWORDS:

• Genome instability
• bladder cancer
• long non-coding rnas
• tcga
• geo

Acknowledgements

This work was supported by the 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).

Dat availability statement

All the data sets of this study are available in the TCGA database(https://portal.gdc.cancer.gov/) and GEO database (http://www.ncbi.nlm.nih.gov/geo/).

Author contributions

L.Z. and L.F.Z. were responsible for conceiving and designing this study, H.W. and Z.Y.Z. wrote the main manuscript, S.L.G. and was responsible for preparing the tables, C.L. and Z.Z. were responsible for preparing figures, and H.W. and X.Y.X. were responsible for re-examination. All authors approved the submission of this study.

Disclosure of potential conflicts of interest

The authors declare that they have no competing interests.

Supplementary materials

Supplemental data for this article can be accessed here.

Additional information

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).