Establishment and Evaluation of a 6-Gene Survival Risk Assessment Model Related to Lung Adenocarcinoma Microenvironment

Biomed Res Int. 2020 Apr 3:2020:6472153. doi: 10.1155/2020/6472153. eCollection 2020.

Abstract

Objective: A survival risk assessment model associated with a lung adenocarcinoma (LUAD) microenvironment was established and evaluated to identify effective independent prognostic factors for LUAD.

Methods: The public data were downloaded from the TCGA database, and ESTIMATE prediction software was used to score immune cells and stromal cells for tumor purity prediction. The samples were divided into the high-score group and the low-score group by the median value of the immune score (or stromal score). The Wilcoxon test was used for differential analysis. GO and KEGG enrichment analysis of differentially expressed genes (DEGs) was performed using "clusterProfiler" of R package. Meanwhile, univariate and multivariate regression analysis was performed on DEGs to construct a multivariate Cox risk regression model with variable gene expression levels as independent prognostic factors affecting a tumor microenvironment (TME) and tumor immunity.

Results: This study found that LUAD patients with high immune cell (stromal cell) infiltration had better prognosis and were in earlier staging. Functional enrichment analysis revealed that most DEGs were related to the proliferation and activation of immune cells or stromal cells. A survival prediction model composed of 6 TME-related genes (CLEC17A, TAGAP, ABCC8, BCAN, FLT3, and CCR2) was established, and finally, the 6 feature genes closely related to the prognosis of LUAD were proved. The AUC value of the ROC curve in this model was 0.7, indicating that the model was reliable.

Conclusion: Six genes related to the LUAD microenvironment have a predictive prognostic value in LUAD.

MeSH terms

  • Adenocarcinoma of Lung / diagnosis*
  • Adenocarcinoma of Lung / genetics*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brevican / genetics
  • Brevican / metabolism
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics*
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism
  • Risk Assessment
  • Sulfonylurea Receptors / genetics
  • Sulfonylurea Receptors / metabolism
  • Tumor Microenvironment
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • ABCC8 protein, human
  • BCAN protein, human
  • Biomarkers, Tumor
  • Brevican
  • CCR2 protein, human
  • CLEC17A protein, human
  • GTPase-Activating Proteins
  • Lectins, C-Type
  • Receptors, CCR2
  • Sulfonylurea Receptors
  • TAGAP protein, human
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3