Identification of an immune-related long non-coding RNA signature and nomogram as prognostic target for muscle-invasive bladder cancer

Aging (Albany NY). 2020 Jun 24;12(12):12051-12073. doi: 10.18632/aging.103369. Epub 2020 Jun 24.

Abstract

To identify an immune-related prognostic signature based on long non-coding RNAs (lncRNAs) and find immunotherapeutic targets for bladder urothelial carcinoma, we downloaded RNA-sequencing data from The Cancer Genome Atlas (TCGA) dataset. Functional enrichment analysis demonstrated bladder urothelial carcinoma was related to immune-related functions. We obtained 332 immune-related genes and 262 lncRNAs targeting immune-related genes. We constructed a signature based on eight lncRNAs in training cohort. Patients were classified as high-risk and low-risk according to signature risk score. High-risk patients had poor overall survival compared with low-risk patients (P < 0.001). Multivariate Cox regression suggested the signature was an independent prognostic indicator. The findings were further validated in testing, entire TCGA and external validation cohorts. Gene set enrichment analysis indicated significant enrichment of immune-related phenotype in high-risk group. Immunohistochemistry and online analyses validated the functions of 4 key immune-related genes (LIG1, TBX1, CTSG and CXCL12) in bladder urothelial carcinoma. Nomogram proved to be a good classifier for muscle-invasive bladder cancer through combining the signature. In conclusion, our immune-related prognostic signature and nomogram provided prognostic indicators and potential immunotherapeutic targets for muscle-invasive bladder cancer.

Keywords: immune-related; lncRNA signature; muscle-invasive bladder cancer; nomogram; prognostic model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / immunology
  • Carcinoma, Transitional Cell / mortality*
  • Carcinoma, Transitional Cell / pathology
  • Cathepsin G / genetics
  • Cathepsin G / immunology
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / immunology
  • DNA Ligase ATP / genetics
  • DNA Ligase ATP / immunology
  • Datasets as Topic
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Muscles / immunology
  • Muscles / pathology
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / immunology
  • Nomograms*
  • Predictive Value of Tests
  • RNA, Long Noncoding / metabolism*
  • RNA-Seq
  • ROC Curve
  • Risk Factors
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology
  • Transcriptome / immunology
  • Urinary Bladder / immunology
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / mortality*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • CXCL12 protein, human
  • Chemokine CXCL12
  • LIG1 protein, human
  • RNA, Long Noncoding
  • T-Box Domain Proteins
  • TBX1 protein, human
  • CTSG protein, human
  • Cathepsin G
  • DNA Ligase ATP