Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Division of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Target Oncol. 2018 Jun;13(3):371-378. doi: 10.1007/s11523-018-0563-4.
The expression level of signal transducer and activator of transcription 3 (STAT3) in tumor cells is reported to associate with response to therapy and with survival time in various types of cancer.
This retrospective study aimed to elucidate the association of STAT3 expression in tumor cells with the therapeutic outcomes of sunitinib in patients with renal cell carcinoma (RCC).
Patients with metastatic RCC who received sunitinib therapy were enrolled in this study. All patients underwent nephrectomy for RCC, and nephrectomy specimens were stained for STAT3 and phosphorylated STAT3 (p-STAT3) by immunohistochemistry.
We assessed 51 patients receiving sunitinib as a first-line therapy. STAT3 expression levels did not influence progression-free survival (PFS) and overall survival (OS); however, patients with p-STAT3-positive tumors exhibited significantly worse PFS compared with those with p-STAT3-negative tumors (log-rank test, P = 0.034). OS tended to be prolonged in patients with p-STAT3-negative tumors. Objective response rate or disease control rate based on the best overall response did not show a significant association with STAT3 or p-STAT3 expression. Univariate Cox proportional hazard regression analyses for clinical predictors revealed that p-STAT3 positivity significantly correlated with shorter PFS (hazard ratio [HR], 2.22, P = 0.041), whereas p-STAT3 expression was not related to the OS.
Activated STAT3 in tumor tissues shows a significant association with poor prognosis in patients with RCC who received sunitinib as a first-line therapy, and positive p-STAT3 expression could be a potential biomarker for refractoriness to sunitinib therapy.
据报道，肿瘤细胞中信号转导和转录激活因子 3（STAT3）的表达水平与各种癌症的治疗反应和生存时间有关。
本回顾性研究旨在阐明肿瘤细胞中 STAT3 表达与接受舒尼替尼治疗的肾细胞癌（RCC）患者治疗结果的相关性。
本研究纳入了接受舒尼替尼治疗的转移性 RCC 患者。所有患者均因 RCC 行肾切除术，采用免疫组织化学法对 STAT3 和磷酸化 STAT3（p-STAT3）进行染色。
我们评估了 51 例接受舒尼替尼作为一线治疗的患者。STAT3 表达水平不影响无进展生存期（PFS）和总生存期（OS）；然而，p-STAT3 阳性肿瘤患者的 PFS 明显短于 p-STAT3 阴性肿瘤患者（对数秩检验，P=0.034）。p-STAT3 阴性肿瘤患者的 OS 倾向于延长。基于最佳总体反应的客观缓解率或疾病控制率与 STAT3 或 p-STAT3 表达无显著相关性。临床预测因素的单因素 Cox 比例风险回归分析显示，p-STAT3 阳性与 PFS 缩短显著相关（风险比[HR]，2.22，P=0.041），而 p-STAT3 表达与 OS 无关。
肿瘤组织中激活的 STAT3 与接受舒尼替尼作为一线治疗的 RCC 患者预后不良显著相关，p-STAT3 阳性表达可能是对舒尼替尼治疗耐药的潜在生物标志物。
