Identification of CD37, cystatin A, and IL-23A gene expression in association with brain metastasis: analysis of a prospective trial

Int J Biol Markers. 2019 Mar;34(1):90-97. doi: 10.1177/1724600818803104. Epub 2019 Mar 10.


Purpose/objectives: We aimed to assess the predictive value of a lung cancer gene panel for the development of brain metastases.

Materials/methods: Between 2011 and 2015, 102 patients with lung cancer were prospectively enrolled in a clinical trial in which a diagnostic fine-needle aspirate was obtained. Gene expression was conducted on all samples that rendered a diagnosis of non-small cell lung cancer (NSCLC). Subsequent retrospective analysis of brain metastases-related outcomes was performed by reviewing patient electronic medical records. A competing risk multivariable regression was performed to estimate the adjusted hazard ratio for the development of brain metastases and non-brain metastases from NSCLC.

Results: A total of 49 of 102 patients had died by the last follow-up. Median time of follow-up was 13 months (range 0.23-67 months). A total of 17 patients developed brain metastases. Median survival time after diagnosis of brain metastases was 3.58 months (95% confidence interval (CI) 2.17, not available). A total of 30 patients developed metastases without any evidence of brain metastases until the time of death or last follow-up. Competing risk analysis identified three genes that were downregulated differentially in the patients with brain metastases versus non-brain metastatic disease: CD37 (0.017), cystatin A (0.022), and IL-23A (0.027). Other factors associated with brain metastases include: stage T ( P ⩽ 8.3e-6) and stage N ( P= 6.8e-4).

Conclusions: We have identified three genes, CD37, cystatin A, and IL-23A, for which downregulation of gene expression was associated with a greater propensity for developing brain metastases. Validation of these biomarkers could have implications on surveillance patterns in patients with brain metastases from NSCLC.

Keywords: Lung cancer; brain metastases; gene expression; non-small cell lung cancer; survival.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Aged
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary
  • Cystatin A / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-23 Subunit p19 / metabolism*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate
  • Tetraspanins / metabolism*


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CD37 protein, human
  • Cystatin A
  • IL23A protein, human
  • Interleukin-23 Subunit p19
  • Tetraspanins
  • CSTA protein, human