STAT3 serine 727 phosphorylation influences clinical outcome in glioblastoma.

ABSTRACT

Besides STAT3 tyrosine 705 phosphorylation (pTyr705-STAT3), phosphorylation of STAT3 at serine 727 (pSer727-STAT3) is shown to contribute to tumorigenesis and be closely related with resistance to radiotherapy and chemotherapy in glioma, but there is currently no study regarding its relevance to prognosis in glioblastoma (GBM). Here, the expression of phosphorylated STAT3 was detected in tumor specimens from 88 patients with newly diagnosed GBM by immunohistochemistry, the Kaplan-Meier survival curve and COX proportional hazards regression model were applied to estimate its influences on progression-free survival (PFS) and overall survival (OS). Immunohistochemical assay showed elevated expression of pSer727-STAT3 in GBM compared with normal brain tissue. Univariate analysis indicated significant correlations of high percentage of pSer727-STAT3 positive tumor cells with shorter PFS (P = 0.006) and OS (P = 0.002). In multivariate analysis, high pSer727-STAT3 expression was demonstrated as an independent unfavorable prognostic indicator for PFS (HR 1.830, P = 0.022) and OS (HR 1.797, P = 0.040). And patients with high expression of both pTyr705-STAT3 and pSer727-STAT3 had a poorer prognosis compared with the remainder (P < 0.005). In conclusion, the high proportion of pSer727-STAT3 positive neoplastic cells in GBM is an independent unfavorable prognostic factor, and increased expression of both pTyr705-STAT3 and pSer727-STAT3 is predictive of poorer clinical outcome, thereby adding to the growing evidence that STAT3 inhibition may be a potential therapeutic strategy in glioblastoma.