Correlation Analysis of JAK-STAT Pathway Components on Prognosis of Patients with Prostate Cancer

Abstract

Janus kinases (JAK)/signal transducers and activator of transcription (STAT) pathway is activated constitutively in prostate cancer (PCa). Despite previous reports implying a role of this pathway in the development of clinical hormone-refractory PCa, the correlation of pathway members with the clinicopathologic features and prognosis of patients with PCa has not been elucidated. To address this problem, pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) were evaluated by immunostaining in needle biopsies of the prostate from 202 PCa patients treated by definitive therapy (105 cases) or hormonal therapy (97 cases). The correlation of two protein expression with the clinicopathologic features and the prognosis of PCa were subsequently assessed. The expression levels of pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) were both positively correlated with Gleason score and clinical stage of patients with PCa. Their expression was also significantly higher in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (both P < 0.001). In all patients, the recurrence-free survival (RFS) rates were significantly higher in those with low pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) expression than that in those with high expression (both P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with lower pJAK-1(Tyr1022/1023) (P < 0.001 and 0.012, respectively) and pSTAT-3(Tyr705) expression (P < 0.001 and 0.015, respectively) were significantly higher than in those with higher expression. Cox multivariate analysis showed that the expression levels of pJAK-1(Tyr1022/1023) (P = 0.002) and pSTAT-3(Tyr705) (P = 0.005) were prognostic factors for PCa in addition to extraprostatic extension (P = 0.026) and Gleason score (P = 0.018). The results of pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) immunostainings in needle-biopsy specimens are prognostic factors for PCa.

Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

“…Importantly, the upregulated STAT3 expression is associated with more malignant behavior of tumor cells and worse prognosis in a variety of human malignancies, such as cancer of lung, prostate, head and neck, ovarian, breast, gastric, pancreas, and thyroid (Wei et al 2003, Masuda et al 2007, Yakata et al 2007, Sheen-Chen et al 2008, Min & Wei-hong 2009, Zhang et al 2011, Ai et al 2012, Liu et al 2012, Dong et al 2014. The increased expression and activation of STAT3 are detected in the tissue specimens of thyroid cancer, including lymphatic metastasis of papillary thyroid cancer in affected patients (Zhang et al 2011, Dong et al 2014.…”

Non-androgen Signaling Pathways in Castration-Resistant Prostate Cancer

“…Interestingly, high levels of STAT3 detected in both malignant and normal surrounding tissues suggesting that the activation of STAT3 may occur prior to any detectable histological changes in the prostate [96]. Furthermore inhibition of this JAK/STAT3 pathway has been reported to induce apoptosis and suppress PCa growth [97]. However, in PCa, BRCA1 can bind STAT3 to promote JAK/STAT3 activation.…”

Role of STAT3 pathway in genitourinary tumors

“…Activated STAT3 signaling is associated with the clinicopathologic characteristics of PCa, such as high pathological stage and Gleason score [60,61]. In addition, the expression levels of STAT3 activator IL-6 are increased in patients with metastatic PCa compared with patients with nonmalignant diseases [62–64].…”