Network models of prostate cancer immune microenvironments identify ROMO1 as heterogeneity and prognostic marker

Sci Rep. 2022 Jan 7;12(1):192. doi: 10.1038/s41598-021-03946-w.

Abstract

Prostate cancer (PCa) is the fifth leading cause of death from cancer in men worldwide. Its treatment remains challenging due to the heterogeneity of the tumor, mainly because of the lack of effective and targeted prognostic markers at the system biology level. First, the data were retrieved from TCGA dataset, and valid samples were obtained by consistent clustering and principal component analysis; next, key genes were analyzed for prognosis of PCa using WGCNA, MEGENA, and LASSO Cox regression model analysis, while key genes were screened based on disease-free survival significance. Finally, TIMER data were selected to explore the relationship between genes and tumor immune infiltration, and GSCAlite was used to explore the small-molecule targeted drugs that act with them. Here, we used tumor subtype analysis and an energetic co-expression network algorithm of WGCNA and MEGENA to identify a signal dominated by the ROMO1 to predict PCa prognosis. Cox regression analysis of ROMO1 was an independent influence, and the prognostic value of this biomarker was validated in the training set, the validated data itself, and external data, respectively. This biomarker correlates with tumor immune infiltration and has a high degree of infiltration, poor prognosis, and strong correlation with CD8+T cells. Gene function annotation and other analyses also implied a potential molecular mechanism for ROMO1. In conclusion, we putative ROMO1 as a portal key prognostic gene for the diagnosis and prognosis of PCa, which provides new insights into the diagnosis and treatment of PCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Cluster Analysis
  • Databases, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Genetic Heterogeneity*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Principal Component Analysis
  • Progression-Free Survival
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / therapy
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • Mitochondrial Proteins
  • ROMO1 protein, human