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

Kazuhiro Yamamoto, Takeshi Ioroi, Kazuya Kanaya, Kazuaki Shinomiya, Shiho Komoto, Sachi Hirata, Kenichi Harada, Aimi Watanabe, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Hideaki Miyake, Masato Fujisawa, Midori Hirai

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article number24
Pages (from-to)1-7
Number of pages7
JournalMedical Oncology
Volume33
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • Multitargeted tyrosine kinase inhibitors
  • Renal cell carcinoma
  • Signal transducer and activator of transcription 3
  • rs4796793 genotype

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Yamamoto, K., Ioroi, T., Kanaya, K., Shinomiya, K., Komoto, S., Hirata, S., Harada, K., Watanabe, A., Suno, M., Nishioka, T., Kume, M., Makimoto, H., Nakagawa, T., Hirano, T., Miyake, H., Fujisawa, M., & Hirai, M. (2016). STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population. Medical Oncology, 33(3), 1-7. [24]. https://doi.org/10.1007/s12032-016-0733-0