Activation of JAK/STAT signal pathway predicts poor prognosis of patients with gliomas

Abstract

JAK/STAT pathway transmits signals from the cell membrane to the nucleus in response to extracellular growth factors and cytokines. Activation of this pathway has been found in certain types of human tumors. The goal of this study was to investigate the correlation between the JAK/STAT pathway in human gliomas and patients' prognosis, which currently is unknown. Western blotting analysis and immunohistochemical staining were performed to detect JAK-1, phosphorylated JAK-1, and STAT-3 expression patterns in the biopsies from 96 patients with primary gliomas. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Western blotting analysis and immunohistochemical staining both indicated that the expression levels of JAK-1, phosphorylated JAK-1, and STAT-3 in primary glioma tissues were significantly higher than those in normal brain tissues (P < 0.001). Especially, the positive expression rates of JAK-1, phosphorylated JAK-1, and STAT-3 were significantly higher in patients with higher grade (P = 0.001, 0.001, and 0.002, respectively) and lower KPS score (P = 0.01, 0.008, and 0.01, respectively). Statistical analysis showed that patients with gliomas expressing JAK-1 and STAT-3 have lower overall survival rates relative to those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.03), WHO grade (P = 0.008), JAK-1 (P = 0.005), and STAT-3 (P = 0.006) were independent prognosis factors for human gliomas. These results provide convincing evidence for the first time that the JAK/STAT pathway may play a role in the progression of human gliomas. Its activated state might be a potent tool for predicting the clinical prognosis of patients with glioma.