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

• Published in: PloS one 2018-08, Vol.13 (8), p.e0201256-e0201256
• Main Authors: Matsuzaki, Kyosuke, Fujita, Kazutoshi, Hayashi, Yujiro, Matsushita, Makoto, Nojima, Satoshi, Jingushi, Kentaro, Kato, Taigo, Kawashima, Atsunari, Ujike, Takeshi, Nagahara, Akira, Uemura, Motohide, Imamura, Ryoichi, Yamaguchi, Seiji, Fushimi, Hiroaki, Miyamoto, Hiroshi, Morii, Eiichi, Nonomura, Norio
• Format: Article
• Language: English
• Subjects: Apoptosis; Biology and Life Sciences; Bladder cancer; Cancer; Cytokines; DNA microarrays; Gene expression; Genetic aspects; Health risks; Interleukin; Interleukin 6; Kinases; Lymph nodes; Medical prognosis; Medicine; Medicine and Health Sciences; Metastasis; Mortality; Multivariate analysis; Oncology; Pathology; Physical Sciences; Physiological aspects; Prognosis; Proteins; Research and Analysis Methods; Review boards; Risk factors; Solid tumors; Sphingosine 1-phosphate; STAT3; Stat3 protein; Statistics; Transcription; Tumors; University graduates; Urinary tract; Urogenital system; Urologic cancer; Urology; Urothelial carcinoma
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0201256

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.