Abstract 751: Characterization of STAT3 activation in human prostate cancer

Signal transducers and activators of transcription (STATs) were initially associated with cytokine signal transduction pathways but are now also recognized as key modulators of key survival processes in in various cancers. Activation of STAT3 occurs by the binding of various cytokines to its receptors leading to the activation of the JAK/ STAT3 signaling pathway. Interleukin-6 (IL-6) has been implicated in regulating growth of various malignant tumors. Activated IL-6 has also been shown to be elevated in the sera from patients with metastatic prostate cancer, and persistent activation of STAT3 is a common feature. To better characterize the potential role of JAK/STAT3 as a therapeutic target for advanced prostate cancer, we examined expression patterns of activated STAT3 in 111 cases of localized prostate cancer from patients who underwent radical prostatectomy. Association studies were conducted with clinicopathological characteristics and biochemical recurrence. We also analyzed the expression of IL-6/KAK/STAT3 genes from RNA-sequencing data form the Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data set and its association to long-term outcomes. Immunohistochemical analysis revealed that 11.7%, 42.3% and 45.9% of patients had high, moderate or low/negative expression of phosphorylated-STAT3 (Tyr705). Cancerous glands tended to have higher STAT3 expression compared to paired normal adjacent tissue, P=0.088. No correlations were observed between STAT3 expression and clinicopathological parameters. Patients with moderate-high p-STAT3 expression tended to experience shorter times to biochemical recurrence (median time, 15 months) compared to patients with low/negative STAT3 activity, (median time to recurrence not reached, P=0.064). Cluster analysis suggested a trend for decreased disease-free survival for patients with high IL-6/KAK/STAT3 gene expression signature. Our data suggests an association between STAT3 signaling and prostate cancer recurrence and provides clinical evidence to support JAK/STAT3 as a potential therapeutic target for patients with advanced prostate cancer. Citation Format: Marco A. De Velasco, Yuji Hatanaka, Yurie Kura, Naomi Ando, Kazuko Sakai, Koichi Sugimoto, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura. Characterization of STAT3 activation in human prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 751. doi:10.1158/1538-7445.AM2017-751