EGFR expression is linked to osteopontin and Nf-κB signaling in clear cell renal cell carcinoma

K Matušan-Ilijaš1, G Damante, D Fabbro

  • 1Department of Pathology, Rijeka University School of Medicine, Braće Branchetta 20, Rijeka, Croatia.

Abstract

Insights

Epidermal growth factor receptor (EGFR) gene is upregulated in clear cell renal cell carcinoma (CCRCC). EGFR mRNA levels correlate with osteopontin (OPN) and nuclear factor kappa B (NF-κB) mRNA, but protein levels show an inverse relationship.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Epidermal growth factor receptor (EGFR) is a key tyrosine kinase in tumorigenesis.
  • The role of EGFR in renal cancer and its targeted therapies is complex, with conflicting evidence.
  • Osteopontin (OPN) and nuclear factor kappa B (NF-κB) may mediate ligand-independent EGFR activation, potentially causing resistance to EGFR-targeted therapies.

Purpose of the Study:

  • To investigate the relationship between EGFR, OPN, and NF-κB at both mRNA and protein levels in clear cell renal cell carcinoma (CCRCC).
  • To explore potential mechanisms of EGFR activation and resistance in renal cancer.

Main Methods:

  • Immunohistochemistry was used to analyze EGFR, OPN, and p65 NF-κB protein expression in 88 CCRCC samples.
  • Quantitative Real-time PCR analyzed EGFR and OPN mRNA expression in 22 CCRCC samples.
  • Expression levels were compared mutually and with NF-κB protein expression.

Main Results:

  • EGFR mRNA levels were significantly higher in CCRCC compared to normal renal tissue (p = 0.012).
  • Increased EGFR mRNA correlated with higher OPN mRNA and NF-κB activation (p < 0.001 and p = 0.045, respectively).
  • Conversely, high EGFR protein expression showed an inverse association with OPN and NF-κB protein expression (p < 0.001 and p = 0.047, respectively).

Conclusions:

  • The EGFR gene is upregulated in CCRCC, with its expression linked to OPN gene expression and NF-κB signaling.
  • The inverse correlation between OPN and EGFR at the protein level may indicate dynamic changes in EGFR following activation.
  • These findings suggest complex regulatory mechanisms of EGFR signaling in renal cancer progression and treatment response.

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