Identification of vital prognostic genes related to tumor microenvironment in pheochromocytoma and paraganglioma based on weighted gene co-expression network analysis

Aging (Albany NY). 2021 Mar 26;13(7):9976-9990. doi: 10.18632/aging.202754. Epub 2021 Mar 26.

Abstract

Pheochromocytoma and paraganglioma (PCPG) is a rare neuroendocrine tumor. This study aims to identify vital prognostic genes which were associated with PCPG tumor microenvironment (TME). We downloaded transcriptome data of PCPG from TCGA database and calculated the immune scores and stromal scores by using the ESTIMATE algorithm. DEGs related to TMB were then identified. We conducted WGCNA to further extract the TME-related modules. GO, KEGG pathway analysis, and PPI network were performed. Survival analysis was conducted to identify the hub genes associated with the prognosis of PCPG. A total of 150 PCPG samples were included in this study. We obtained 1507 and 2067 DEGs based on immune scores and stromal scores, respectively. WGCNA analysis identified the red module and brown module were correlated with immune sores while the turquoise module and red module were significantly associated with stromal scores. Functional enrichments analysis revealed that 307 TME-related genes were correlated with the inflammation or immune response. Survival analysis showed that three TME-relate genes (ADGRE1, CCL18, and LILRA6) were associated with PCPG prognosis. These three hub genes including ADGRE1, CCL18, and LILRA6 might be involved in the progression of PCPG and could serve as potential biomarkers and novel therapeutic targets.

Keywords: WGCNA; bioinformatic methods; pheochromocytoma and paraganglioma; prognostic; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / genetics*
  • Adrenal Gland Neoplasms / pathology
  • Biomarkers, Tumor / genetics*
  • Calcium-Binding Proteins / genetics
  • Chemokines, CC / genetics
  • Computational Biology
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Paraganglioma / genetics*
  • Paraganglioma / mortality
  • Paraganglioma / pathology
  • Pheochromocytoma / genetics*
  • Pheochromocytoma / mortality
  • Pheochromocytoma / pathology
  • Prognosis
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, Immunologic / genetics
  • Survival Rate
  • Transcriptome
  • Tumor Microenvironment / genetics*

Substances

  • ADGRE1 protein, human
  • Biomarkers, Tumor
  • CCL18 protein, human
  • Calcium-Binding Proteins
  • Chemokines, CC
  • LILRA6 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Immunologic