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

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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.

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Acknowledgements

The authors would like to thank Enago (www.enago.jp) for the English language review.

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Authors and Affiliations

  1. Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Kazuhiro Yamamoto, Tsutomu Nakagawa & Ikuko Yano

  2. Division of Urology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Takuto Hara, Hideaki Miyake & Masato Fujisawa

  3. Division of Pharmaceutics, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Tsutomu Nakagawa, Midori Hirai & Ikuko Yano

  4. Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu city, Shizuoka, 431-3192, Japan

    Hideaki Miyake

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  1. Kazuhiro Yamamoto
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Correspondence to Kazuhiro Yamamoto.

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Funding

This work was supported in part by a research grant from Kurozumi Medical Foundation.

Conflict of Interest

H. Miyake and M. Fujisawa have received lecture fees from Pfizer. K. Yamamoto, T. Hara, T. Nakagawa, M. Hirai, and I. Yano declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Yamamoto, K., Hara, T., Nakagawa, T. et al. Association of Expression Levels or Activation Status of STAT3 with Treatment Outcomes of Sunitinib in Patients with Renal Cell Carcinoma. Targ Oncol 13, 371–378 (2018). https://doi.org/10.1007/s11523-018-0563-4

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  • DOI: https://doi.org/10.1007/s11523-018-0563-4

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