Yamamoto Kazuhiro, Ioroi Takeshi, Kanaya Kazuya, Shinomiya Kazuaki, Komoto Shiho, Hirata Sachi, Harada Kenichi, Watanabe Aimi, Suno Manabu, Nishioka Tatsuya, Kume Manabu, Makimoto Hiroo, Nakagawa Tsutomu, Hirano Takeshi, Miyake Hideaki, Fujisawa Masato, Hirai Midori
Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Division of Pharmacokinetics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Med Oncol. 2016 Mar;33(3):24. doi: 10.1007/s12032-016-0733-0. Epub 2016 Jan 30.
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.
信号转导子和转录激活子（STAT）3是多种酪氨酸激酶抑制剂（mTKI）诱导肾细胞癌（RCC）细胞生长抑制和凋亡的关键因素。本研究旨在确定转移性RCC（mRCC）患者中STAT3基因单核苷酸多态性（SNP）与肿瘤对mTKI反应之间的关联。对71例接受任何mTKI治疗的透明细胞RCC患者进行回顾性基因分型，以阐明STAT3 SNP与药物总体最佳反应之间的潜在关联。在纳入分析的50例患者中，17例观察到部分或完全缓解。发现rs4796793等位基因与肿瘤反应之间存在显著关联[G与C，比值比（OR）3.25，95%置信区间（CI）1.30 - 8.07]。rs4796793处C/C基因型的反应者百分比高于G/C + G/G基因型（OR 4.46，95% CI 1.31 - 15.28）。生存时间分析表明，CC基因型患者与G/C + G/G基因型患者在治疗反应时间上存在统计学显著差异，但在无进展生存期或治疗失败时间上无差异。rs4796793基因型是mRCC患者对mTKI反应的一个新的预测因素。然而，需要更大患者队列的前瞻性转化试验来证实这些结果。
