A gene expression-based immune signature for lung adenocarcinoma prognosis

Cancer Immunol Immunother. 2020 Sep;69(9):1881-1890. doi: 10.1007/s00262-020-02595-8. Epub 2020 May 5.


Background: Lung adenocarcinoma (LUAD) has become the most frequent histologic type of lung cancer in the past several decades. Recent successes with immune checkpoint blockade therapy have demonstrated that the manipulation of the immune system is a very potent treatment for LUAD. This study aims to explore the role of immune-related genes in the development of LUAD and establish a signature that can predict overall survival for LUAD patients.

Methods: To identify the differential expression genes (DEGs) between normal and tumor tissues, we developed an analysis strategy to combine an independent-sample design and a paired-sample design using RNA-seq transcriptomic profiling data of The Cancer Genome Atlas LUAD samples. Further, we selected prognostic markers from DEGs and evaluated their prognostic value in a prediction model.

Results: We identified and validated PD1, PDL1 and CTLA4 genes as prognostic markers, which are well-known immune checkpoints, and revealed two new potential prognostic immune checkpoints for LUAD, HHLA2 (logFC = 2.55, FDR = 1.89 × 10-6) and VTCN1 (logFC = -2.86, FDR = 1.72 × 10-11). Furthermore, we identified an 18-gene LUAD prognostic biomarker panel and observed that the classified high-risk group presented a significantly shorter overall survival time (HR = 3.57, p value = 4.07 × 10-10). The prediction model was validated in five independent high-throughput gene expression datasets.

Conclusions: The identified DEG features may serve as potential biomarkers for prognosis prediction of LUAD patients and immunotherapy. Based on that assumption, we identified a gene expression-based immune signature for lung adenocarcinoma prognosis.

Keywords: Differential expression; Immunotherapy; Lung adenocarcinoma; Pathway enrichment; Prognosis.

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / immunology*
  • Aged
  • Biomarkers, Tumor / immunology
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology*
  • Male
  • Prognosis
  • Transcriptome / genetics*
  • Transcriptome / immunology*


  • Biomarkers, Tumor