Immune profile of the tumor microenvironment and the identification of a four-gene signature for lung adenocarcinoma

Aging (Albany NY). 2020 Dec 9;13(2):2397-2417. doi: 10.18632/aging.202269. Epub 2020 Dec 9.

Abstract

The composition and relative abundances of immune cells in the tumor microenvironment are key factors affecting the progression of lung adenocarcinomas (LUADs) and the efficacy of immunotherapy. Using the cancer gene expression dataset from The Cancer Genome Atlas (TCGA) program, we scored stromal and immune cells for tumor purity prediction by CIBERSORT and ESTMATE. Differential expression analysis was employed to identify 374 genes between the high-score group and the low-score group, which were utilized to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein-protein interaction (PPI) and Cox regression analysis were performed on the differentially expressed genes (DEGs) to identify four key tumor microenvironment (TME) -related genes (CCR2, CCR4, P2RY12, and P2RY13). The expression levels of the four DEGs differed significantly among LUAD patients of different ages, genders, and TNM stages. We found that the infiltration of resting memory CD4+ T cells, memory B cells, and M0 macrophages into the TME was co-regulated by these four DEGs. These four genes were closely related to the prognosis of LUAD and affected the infiltration of immune cells into the TME, which had predictive prognostic value in LUAD.

Keywords: immune cell infiltration; lung adenocarcinoma; tumor immunity; tumor microenvironment; tumor stroma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / pathology
  • Aged
  • Biomarkers, Tumor / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, CCR2 / genetics
  • Receptors, CCR4 / genetics
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2Y12 / genetics
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor
  • CCR2 protein, human
  • CCR4 protein, human
  • P2RY12 protein, human
  • P2RY13 protein, human
  • Receptors, CCR2
  • Receptors, CCR4
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y12