Association of Expression Levels or Activation Status of STAT3 with Treatment Outcomes of Sunitinib in Patients with Renal Cell Carcinoma

Abstract

Background: The expression level of signal transducer and activator of transcription 3 (STAT3) in tumor cells is reported to associate with response to therapy and with survival time in various types of cancer.

Objective: This retrospective study aimed to elucidate the association of STAT3 expression in tumor cells with the therapeutic outcomes of sunitinib in patients with renal cell carcinoma (RCC).

Patients and methods: Patients with metastatic RCC who received sunitinib therapy were enrolled in this study. All patients underwent nephrectomy for RCC, and nephrectomy specimens were stained for STAT3 and phosphorylated STAT3 (p-STAT3) by immunohistochemistry.

Results: We assessed 51 patients receiving sunitinib as a first-line therapy. STAT3 expression levels did not influence progression-free survival (PFS) and overall survival (OS); however, patients with p-STAT3-positive tumors exhibited significantly worse PFS compared with those with p-STAT3-negative tumors (log-rank test, P = 0.034). OS tended to be prolonged in patients with p-STAT3-negative tumors. Objective response rate or disease control rate based on the best overall response did not show a significant association with STAT3 or p-STAT3 expression. Univariate Cox proportional hazard regression analyses for clinical predictors revealed that p-STAT3 positivity significantly correlated with shorter PFS (hazard ratio [HR], 2.22, P = 0.041), whereas p-STAT3 expression was not related to the OS.

Conclusions: Activated STAT3 in tumor tissues shows a significant association with poor prognosis in patients with RCC who received sunitinib as a first-line therapy, and positive p-STAT3 expression could be a potential biomarker for refractoriness to sunitinib therapy.