Construction of an Immune-Associated Gene-Based Signature in Muscle-Invasive Bladder Cancer

Dis Markers. 2020 Dec 29:2020:8866730. doi: 10.1155/2020/8866730. eCollection 2020.

Abstract

Background: In recent years, immune-associated genes (IAGs) have been documented as having critical roles in the occurrence and progression of muscle-invasive bladder cancer (MIBC). Novel immune-related biomarkers and a robust prognostic signature for MIBC patients are still limited. The study is aimed at developing an IAG-based signature to predict the prognosis of MIBC patients.

Methods: In the present study, we identified differentially expressed IAGs in MIBC by using transcriptomics data from The Cancer Genome Atlas (TCGA) database and proteomics data from our samples. We further constructed an IAG-based signature and evaluated its prognostic and predictive value by survival analysis and nomogram. Tumor Immune Estimation Resource (TIMER) was applied to explore the correlation between the IAG-based signature and immune cell infiltration in the microenvironment of MIBC.

Results: A total of 22 differentially expressed IAGs were identified, and 2 IAGs (NR2F6 and AHNAK) were used to establish a prognostic signature. Subsequently, survival analysis showed that high-risk scores were significantly correlated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of MIBC patients. A prognostic nomogram was constructed by integrating clinical factors with the IAG-based signature risk score. In addition, the IAG-based signature risk score was positively associated with the infiltration of macrophages and dendritic cells in MIBC.

Conclusions: We constructed and verified a novel IAG-based signature, which could predict the prognosis of MIBC and might reflect the status of the immune microenvironment of MIBC. Further studies in more independent clinical cohorts and further experimental exploration of the prognostic IAG-based signature are still needed.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Annexin A6 / genetics
  • Annexin A6 / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Middle Aged
  • Muscles / pathology
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proteome / genetics
  • Proteome / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Survival Analysis
  • Transcriptome
  • Tumor Microenvironment / immunology*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology

Substances

  • AHNAK protein, human
  • Annexin A6
  • Biomarkers, Tumor
  • Membrane Proteins
  • NR2F6 protein, human
  • Neoplasm Proteins
  • Proteome
  • Repressor Proteins
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases