Characterizing heterogeneity of non-small cell lung tumour microenvironment to identify signature prognostic genes

J Cell Mol Med. 2020 Dec;24(24):14608-14618. doi: 10.1111/jcmm.16092. Epub 2020 Nov 12.

Abstract

Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in non-small cell lung cancer (NSCLC). This study focused on the characterization of immune infiltration profiling in patients with NSCLC and its correlation with survival outcome. All TCGA samples were divided into three heterogeneous clusters based on immune cell profiles: cluster 1 ('low infiltration' cluster), cluster 2 ('heterogeneous infiltration' cluster) and cluster 3 ('high infiltration' cluster). The immune cells were responsible for a significantly favourable prognosis for the 'high infiltration' community. Cluster 1 had the lowest cytotoxic activity, tumour-infiltrating lymphocytes and interferon-gamma (IFN-γ), as well as immune checkpoint molecules expressions. In addition, MHC-I and immune co-stimulator were also found to have lower cluster 1 expressions, indicating a possible immune escape mechanism. A total of 43 differentially expressed genes (DEGs) that overlapped among the groups were determined based on three clusters. Finally, based on a univariate Cox regression model, prognostic immune-related genes were identified and combined to construct a risk score model able to predict overall survival (OS) rates in the validation datasets.

Keywords: non-small cell lung cancer; prognostic; tumour microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Computational Biology / methods
  • Databases, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Phenotype
  • Prognosis
  • Reproducibility of Results
  • Transcriptome
  • Tumor Microenvironment* / genetics
  • Tumor Microenvironment* / immunology

Substances

  • Biomarkers, Tumor