STAT3 Tyr705 phosphorylation affects clinical outcome in patients with newly diagnosed supratentorial glioblastoma

Abstract

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.