CD44 Is Involved in Sunitinib Resistance and Poor Progression-free Survival After Sunitinib Treatment of Renal Cell Carcinoma

Anticancer Res. 2021 Oct;41(10):4875-4883. doi: 10.21873/anticanres.15301.

Abstract

Background/aim: Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study aimed to examine the role of CD44 in sunitinib resistance and as a predictive marker in mRCC.

Materials and methods: We analyzed the effect of CD44 knockdown on sunitinib resistance in RCC cell lines using WST-1 assays. CD44 expression in mRCC patients treated with first-line sunitinib was determined by immunohistochemistry. We validated the findings of this study by in silico analysis.

Results: CD44 knockdown increased sensitivity to sunitinib. Immunohistochemical analysis revealed that 19 (34.5%) of 55 mRCC cases were positive for CD44. CD44-positive cases were associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, high CD44 expression was significantly associated with poor PFS after sunitinib but not after avelumab + axitinib therapy.

Conclusion: CD44 is involved in sunitinib resistance and may be a promising marker for sunitinib treatment in mRCC.

Keywords: CD44; in silico analysis; renal cell carcinoma; sunitinib.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality*
  • Carcinoma, Renal Cell / pathology
  • Drug Resistance, Neoplasm*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Sunitinib / pharmacology*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Sunitinib