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

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.

SUBMITTER: Matsuzaki K

PROVIDER: S-EPMC6084864 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The aim of this study was to investigate the effect of preoperative anemia on the prognosis of patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).A total of 620 patients with UTUC were retrospectively analyzed. Anemia was decided by preoperatively measured hemoglobin values based on the World Health Organization (WHO) classification. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze the relationship between anemia and survival outcomes. The meta-analysis part was performed according to PRISMA guidelines.The median follow-up was 51 (range: 1-168) months. A total of 246 patients had preoperative anemia in our cohort. Anemia was found to be related to high-grade (P < .001), sessile architecture (P = .001), advanced T stage (P < .001), lymphovascular invasion (LVI) (P = .006), and worse chronic kidney disease (CKD) stage (P = .012). Kaplan-Meier curves revealed that patients with preoperative anemia had worse overall survival (OS), cancer-specific survival (CSS), and disease recurrence-free survival (RFS) (all P < .001). Multivariable Cox analyses found that anemia was an independent predictor of CSS [hazard ratio (HR) 1.719, 95% confidence interval (95% CI): 1.285-2.300], RFS (HR 1.427, 95% CI: 1.114-1.829) and OS (HR 1.756, 95% CI: 1.353-2.279). Among patients without end-stage renal disease (ESRD, n = 614), the anemia was also proved to be associated with worse outcomes in multivariable Cox analysis (OS, HR 1.759, 95% CI: 1.353-2.287; CSS, HR 1.726, 95% CI: 1.289-2.311, and RFS, HR 1.431, 95% CI: 1.117-1.837). Seven studies were included in the meta-analysis, and the pooled results showed that anemia was also related to worse CSS (HR 2.05, 95% CI: 1.73-2.44), RFS (HR 1.57, 95% CI: 1.30-1.90), and OS (HR 1.53, 95% CI: 1.10-2.13), but not related to intravesical recurrence (HR 1.17, 95% CI: 0.75-1.82).Preoperative anemia was proved to be significantly associated with worse oncologic outcomes in patients with UTUC following RNU.

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

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