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Increased Expression of AXL and c-MET in High-Grade Clear Cell Renal Cell Carcinoma and Its Association With

Shuji Mikami1,2, Ryuichi Mizuno3, Nobuyuki Tanaka3

  • 1Department of Pathology, Keio University School of Medicine, Tokyo, Japan.

Pathology International
|June 2, 2025
PubMed

Insights

Cabozantinib shows promise for advanced renal cell carcinoma (RCC). Researchers found that AXL and c-MET molecules are key in ccRCC progression and resistance to sunitinib, potentially influencing treatment response.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Cabozantinib, a VEGFR-TKI, is effective for advanced renal cell carcinoma (RCC).
  • The precise mechanisms behind cabozantinib's superior efficacy compared to other treatments are not fully understood.
  • Cabozantinib targets VEGFR, AXL, and c-MET.

Purpose of the Study:

  • To investigate the roles of AXL and c-MET in clear cell renal cell carcinoma (ccRCC) progression.
  • To explore the relationship between AXL, c-MET expression, and response to sunitinib treatment.
  • To examine the impact of c-MET on the tumor immune microenvironment.

Main Methods:

  • Immunohistochemical examination of AXL and c-MET expression in 110 primary ccRCC tissues.
  • Analysis of eight sunitinib-treated primary ccRCC tissues.
  • Correlation analysis between AXL/c-MET expression and clinical/histological parameters, including overall survival and PD-L1 expression.

Main Results:

  • AXL expression correlated with primary tumor stage.
  • c-MET expression correlated with distant metastasis, histological grade, and overall survival.
  • Higher c-MET expression was associated with increased programmed death-ligand 1 (PD-L1)-positive immune cells.
  • AXL and c-MET expression were elevated in sunitinib-treated ccRCC tissues compared to untreated tissues.

Conclusions:

  • AXL and c-MET are implicated in ccRCC progression and resistance to sunitinib.
  • c-MET may influence the tumor immune microenvironment by upregulating PD-L1 expression.
  • These molecular pathways may be relevant to cabozantinib's therapeutic effects in RCC.
Keywords:
AXLPD‐L1cabozantinibc‐METrenal cell carcinomatumor microenvironment

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