An immune gene expression signature distinguishes central nervous system metastases from primary tumours in non-small-cell lung cancer

Eur J Cancer. 2020 Jun:132:24-34. doi: 10.1016/j.ejca.2020.03.014. Epub 2020 Apr 20.


Background: Dissemination of non-small-cell lung cancer (NSCLC) in the central nervous system is a frequent and challenging clinical problem. Systemic or local therapies rarely prolong survival and have modest activity regarding local control. Alterations in gene expression in brain metastasis versus primary tumour may increase aggressiveness and impair therapeutic efforts.

Methods: We identified 25 patients with surgically removed NSCLC brain metastases in two different patient cohorts. For 13 of these patients, primary tumour samples were available. Gene expression analysis using the nCounter® PanCancer Immune Profiling gene expression panel (nanoString technologies Inc.) was performed in brain metastases and primary tumour samples. Identification of differentially expressed genes was conducted on normalized data using the nSolver analysis software.

Results: We compared gene expression patterns in brain metastases with primary tumours. Brain metastasis samples displayed a distinct clustering pattern compared to primary tumour samples with a statistically significant downregulation of genes related to immune response and immune cell activation. Results from KEGG term analysis on differentially expressed genes revealed a concomitant enrichment of multiple KEGG terms associated with the immune system. We identified a 12-gene immune signature that clearly separated brain metastases from primary tumours.

Conclusions: We identified a unique gene downregulation pattern in brain metastases compared with primary tumours. This finding may explain the lower intracranial efficacy of systemic therapy, especially immunotherapy, in brain metastasis of patients with NSCLC.

Keywords: Brain metastases; Gene expression; Immune signature; Matched analyses; Non–small-cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Adenocarcinoma of Lung / therapy
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Large Cell / therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / pathology*
  • Small Cell Lung Carcinoma / therapy
  • Transcriptome*


  • Biomarkers, Tumor