Abstract
Background: Studies have shown that long non-coding RNA (LncRNA) plays a critical role in maintaining genomic instability. The correlation between lncRNA and genomic instability is still worth exploring in bladder cancer as a new tumour marker. Methods: Therefore, combined with the lncRNA expression profile and somatic mutation profile of bladder cancer, we established a computing framework of lncRNA related to genomic instability and identified 58 new lncRNA related to genomic instability. Next, we identified a lncRNA signature (GILncSig), based on these 58 new genes, which divided patients into high-risk and low-risk groups. The clinical prognosis was significantly different and was further verified in an independent cohort of patients. Results: We confirmed that GILncSig is related to the genomic mutation rate of bladder cancer, suggesting that GILncSig can be used as an indicator of genomic instability. The results show that GILncSig has prognostic value independent of age, sex, grade, and stage and is vital in evaluating clinical prognosis. To sum up, this study provides a vital research basis and methods for further exploring the role of lncRNA in the genomic instability of bladder cancer and provides a theoretical basis for the identification of bladder cancer biomarkers related to genomic instability.
Highlights
Bladder cancer is a common malignant tumour of the urinary system
The cumulative number of somatic mutations for each patient was computed; Second, patients were ranked in decreasing order of the cumulative number of somatic mutations; the top 25% of patients were defined as genomic unstable (GU)-like group, and the last 25% were defined genomically stable (GS)-like group; The lncRNAs expression profiles of GU group and GS group were compared by microarray significance analysis (SAM) method; differentially expressed lncRNAs (fold change > 1 or
Based on the functional analysis of the genes co-expressed with 58 lncRNAs associated with genomic instability, our observation showed that the genes co-expressed with the 58 lncRNAs were enriched in the regulation of mitosis
Summary
The American Cancer Society estimates 76,960 new cases and 16,390 bladder cancer deaths in the US with a male: female ratio of 3:1 [1]. There is an urgent need to find new biomarkers to evaluate the clinical prognosis of patients with bladder cancer more accurately. The correlation between lncRNA and genomic instability is still worth exploring in bladder cancer as a new tumour marker. This study provides a vital research basis and methods for further exploring the role of lncRNA in the genomic instability of bladder cancer and provides a theoretical basis for the identification of bladder cancer biomarkers related to genomic instability
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