RNA-Sequencing Data Reveal a Prognostic Four-lncRNA-Based Risk Score for Bladder Urothelial Carcinoma: An in Silico Update

Cell Physiol Biochem. 2018;50(4):1474-1495. doi: 10.1159/000494647. Epub 2018 Oct 25.

Abstract

Background/aims: Current practical advances in high-throughput data technologies including RNA-sequencing have led to the identification of long non-coding RNAs (lncRNAs) for potential clinical application against bladder urothelial cancer (BLCA). However, most previous studies focused on the clinical value of individual lncRNAs, which has limited the potential for future clinical application.

Methods: In this study, RNA-sequencing data of lncRNAs was downloaded from The Cancer Genome Atlas database. Risk score was constructed based on survival-associated lncRNAs identified using differential expression analysis as well as univariate and multivariate Cox proportional hazards regression analysis. Receiver operating characteristic and Kaplan-Meier curve analyses were employed to evaluate the clinical and prognostic value of risk scores. Bioinformatics analyses were used to investigate the potential mechanisms of newly identified lncRNAs.

Results: Among 2,127 differentially expressed lncRNAs (DELs), four new lncRNAs (AC145124.1, AC010168.2, MIR200CHG, and AC098613.1) showed valuable prognostic effects in BLCA patients. More importantly, the four-DEL-based risk score had the potential to become an independent marker for the survival status prediction of BLCA patients. Distinct co-expressed genes and signaling pathways were identified when BLCA was categorized into low- and high-risk groups. Furthermore, a protein-coding gene, HIST4H4 was found only 68 bp from the AC010168.2 DEL. HIST4H4 expression level was evidently up-regulated and positively correlated with AC010168.2 in BLCA patients.

Conclusion: This in silico investigation pioneers the future investigation of the utility of prognostic lncRNAs for BLCA.

Keywords: Bladder urothelial cancer (BLCA); LncRNA; Prognosis; The Cancer Genome Atlas (TCGA).

MeSH terms

  • Area Under Curve
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Kaplan-Meier Estimate
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / metabolism*
  • ROC Curve
  • Risk Factors
  • Sequence Analysis, RNA
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding