Expression of EPHA5 in lung adenocarcinoma is associated with lymph node metastasis and EGFR mutation

APMIS. 2022 Jun;130(6):338-345. doi: 10.1111/apm.13222. Epub 2022 Apr 4.

Abstract

EPHA5 is a member of the Eph family of tyrosine kinase receptors, which affect carcinogenesis. The expression level of the EPHA5 receptor in a set of lung adenocarcinoma tissue samples was checked using immunohistochemistry. The relationship between EPHA5 expression and clinicopathological parameters, and epidermal growth factor receptor (EGFR) and Braf mutations were analyzed. We also checked the expression level of the EPHA5 receptor in four lung cancer cell lines. High expression of EPHA5 was found in NCI-H460 and H1299 cells, while low expression was observed in A549 and SPC-A1 cells. EPHA5 was knocked down in NCI-H460 and H1299 lung cancer cell lines using siRNAs. The proliferation, clone formation, and invasive ability were analyzed in NCI-H460 and H1299 cells with EPHA5 knockdown. The results show that the EPHA5 receptor is differently expressed in lung adenocarcinoma tissues, in which positive and negative expression of EPHA5 was found in 58.1% and 41.9% of tissues, respectively. Positive expression of EPHA5 was associated with lymph node metastasis (p = 0.002), differentiation (p = 0.020), TNM stage (p = 0.002), and EGFR mutation (p = 0.001). The proliferation, clone formation, and invasive ability were significantly decreased after EPHA5 knockdown in NCI-H460 and H1299 cells. Our data suggest that the EPHA5 receptor plays a role in tumor promotion in lung adenocarcinoma and is a potential target for lung adenocarcinoma treatment.

Keywords: EGFR mutation; EPHA5; lung adenocarcinoma; receptor tyrosine kinase.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / pathology
  • ErbB Receptors* / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Lymphatic Metastasis
  • Mutation
  • Receptor, EphA5* / biosynthesis
  • Receptor, EphA5* / genetics

Substances

  • EGFR protein, human
  • EPHA5 protein, human
  • ErbB Receptors
  • Receptor, EphA5