STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population

Abstract

Signal transducer and activator of transcription (STAT) 3 is a key factor in multiple tyrosine kinase inhibitor (mTKI)-induced growth inhibition and apoptosis of renal cell carcinoma (RCC) cells. This study aimed to identify associations between single-nucleotide polymorphisms (SNPs) in the STAT3 gene and tumor response to mTKIs in patients with metastatic RCC (mRCC). Seventy-one patients with clear cell RCC treated with any mTKI were retrospectively genotyped to elucidate a potential association between STAT3 SNPs and overall best response to drugs. Of 50 patients included for analysis, a partial or complete response was observed in 17. A significant association was found between rs4796793 alleles and tumor response [G vs. C, odds ratio (OR) 3.25, 95% confidence interval (CI) 1.30-8.07]. There were a higher percentage of responders with the C/C genotype at rs4796793 than with the G/C+G/G genotypes (OR 4.46, 95% CI 1.31-15.28). Time-to-event analysis demonstrated a statistically significant difference between patients with the CC genotype and those with G/C+G/G genotypes in time-to-treatment response, but not in progression-free survival or time-to-treatment failure. The rs4796793 genotype is a novel predictive factor of the response to mTKIs in patients with mRCC. However, prospective translational trials with larger patient cohorts are required to confirm these results.