STAT3 expression is a prognostic marker in upper urinary tract urothelial carcinoma.

Kyosuke Matsuzaki,Atsunari Kawashima,Norio Nonomura,Kazutoshi Fujita,Kentaro Jingushi,Hiroshi Miyamoto,Ryoichi Imamura,Seiji Yamaguchi,Eiichi Morii,Makoto Matsushita,Satoshi Nojima,Hiroaki Fushimi,Takeshi Ujike,Akira Nagahara,Taigo Kato,Motohide Uemura,Yujiro Hayashi,Salvatore V Pizzo

doi:10.1371/journal.pone.0201256

Abstract

Signal transducer and activator of transcription 3 (STAT3) plays a prominent role in the growth and invasion of several types of solid tumors. In this study, to assess the expression status and prognostic significance of the STAT3 pathway in upper urinary tract urothelial carcinoma (UTUC), we immunohistochemically stained for STAT3 and STAT3 pathway proteins, sphingosine-1-phosphate receptor 1 (S1PR1) and interleukin-6 (IL-6), in a tissue microarray containing 99 UTUC specimens. There were no significant associations between STAT3, S1PR1, or IL-6 expression pattern and tumor grade or pT stage. However, the patients with high STAT3 tumor had a significantly higher risk of both disease progression (p = 0.009) and cancer-specific mortality (p = 0.009), but not with tumors expressing S1PR1 or IL-6. High STAT3 expression in the nucleus was also associated with a significantly higher risk of both disease progression (p = 0.003) and cancer-specific mortality (p = 0.034). Multivariate analysis revealed that high STAT3 expression in the nucleus was significantly associated with cancer-specific survival after adjustment for pathological stage, lymph node involvement, lymphovascular invasion, and tumor grade (HR = 2.136, 95% CI = 1.009–4.767, p = 0.047). Our findings indicated that STAT3 could be a cancer-promoting factor and potentially a significant prognostic factor in UTUC.

Highlights

Upper urinary tract urothelial carcinoma (UTUC) is relatively rare, accounting for approximately 5% to 10% of all urothelial tumors of the urinary tract [1,2,3]
Signal transducer and activator of transcription 3 (STAT3) expression is a prognostic marker in upper urinary tract urothelial carcinoma compared with bladder cancer, little is known about the molecular markers confirmed to be useful for daily clinical decision making
We evaluated nuclear STAT3 expression by multivariate analysis, which revealed it to be significantly associated with cancer-specific survival after adjustment for pathological stage, lymph node involvement, lymphovascular invasion, and tumor grade

Summary

Introduction

Upper urinary tract urothelial carcinoma (UTUC) is relatively rare, accounting for approximately 5% to 10% of all urothelial tumors of the urinary tract [1,2,3]. Urothelial carcinoma of the bladder and UTUC share many characteristics, practical, anatomical, biological, and molecular differences have been proven [4, 5]. STAT3 expression is a prognostic marker in upper urinary tract urothelial carcinoma compared with bladder cancer, little is known about the molecular markers confirmed to be useful for daily clinical decision making. In response to cytokines and growth factors, STAT3 is phosphorylated by receptor-associated Janus kinases (JAK), forms homo- or hetero-dimers, and translocates to the nucleus where it acts as a transcription activator [8]

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Discussion

Conclusion