Lin Guo-Shi, Yang Li-Juan, Wang Xing-Fu, Chen Yu-Peng, Tang Wen-Long, Chen Long, Lin Zhi-Xiong
Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Med Oncol. 2014 Apr;31(4):924. doi: 10.1007/s12032-014-0924-5. Epub 2014 Mar 21.
STAT3 tyrosine705 phosphorylation (p-STAT3, Tyr705), a molecular hub for several signal transduction pathways of glioma, plays a central role in glioblastoma (GBM) carcinogenesis and progression. However, it is still controversial whether p-STAT3 expression is associated with the clinical outcome of patients with glioblastoma. Such evidence would contribute to further illustrate whether STAT3 inhibition is suitable for clinical treatment. Here, we examined the expression of p-STAT3 in the tumor tissues from 90 patients with newly diagnosed supratentorial GBM via immunohistochemical technique and evaluated the influences of its expression on progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier curve and COX proportional hazards regression model. Immunohistochemical assay indicated increased expression of p-STAT3 in GBM tissue compared to adjacent normal brain tissue without p-STAT3 expression. There were no observed associations between p-STAT3 expression and patients' gender (P = 0.660), age (P = 0.867) or preoperative Karnofsky Performance Status (KPS) (P = 0.121). Univariate survival analysis revealed significant correlations of high p-STAT3 expression with shorter PFS (P = 0.012) and OS (P = 0.009). Multivariate survival analysis confirmed high p-STAT3 expression as a significant prognostic indicator for shorter PFS (HR 2.158, P = 0.019) and OS (HR 2.120, P = 0.031), independent of age, KPS and chemoradiotherapy. In summary, the high percentage of p-STAT3 positive tumor cells is a significant independent prognostic indicator for poor clinical outcome in patients with GBM, in addition to advanced age, poor performance status and nonstandard chemoradiotherapy, suggesting that STAT3 might be as a promising therapeutic target in GBM.
信号转导与转录激活因子3（STAT3）酪氨酸705位点磷酸化（p-STAT3，Tyr705）是胶质瘤多种信号转导途径的分子枢纽，在胶质母细胞瘤（GBM）的发生发展中起核心作用。然而，p-STAT3的表达与胶质母细胞瘤患者的临床预后是否相关仍存在争议。此类证据将有助于进一步阐明抑制STAT3是否适用于临床治疗。在此，我们通过免疫组化技术检测了90例新诊断的幕上GBM患者肿瘤组织中p-STAT3的表达，并使用Kaplan-Meier曲线和COX比例风险回归模型评估其表达对无进展生存期（PFS）和总生存期（OS）的影响。免疫组化分析表明，与无p-STAT3表达的相邻正常脑组织相比，GBM组织中p-STAT3的表达增加。未观察到p-STAT3表达与患者性别（P = 0.660）、年龄（P = 0.867）或术前卡氏评分（KPS）（P = 0.121）之间存在关联。单因素生存分析显示，p-STAT3高表达与较短的PFS（P = 0.012）和OS（P = 0.009）显著相关。多因素生存分析证实，p-STAT3高表达是PFS缩短（HR 2.158，P = 0.019）和OS缩短（HR 2.120，P = 0.031）的显著预后指标，独立于年龄、KPS和放化疗。总之，除了高龄、身体状况差和放化疗不规范外，p-STAT3阳性肿瘤细胞比例高是GBM患者临床预后不良的显著独立预后指标，提示STAT3可能是GBM中有前景的治疗靶点。
