Skip to main content
Top
Published in: Targeted Oncology 3/2018

01-06-2018 | Original Research Article

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

Authors: Kazuhiro Yamamoto, Takuto Hara, Tsutomu Nakagawa, Midori Hirai, Hideaki Miyake, Masato Fujisawa, Ikuko Yano

Published in: Targeted Oncology | Issue 3/2018

Login to get access

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.
Literature
5.
go back to reference Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell. 1999;98:295–303.CrossRefPubMed Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, et al. Stat3 as an oncogene. Cell. 1999;98:295–303.CrossRefPubMed
17.
go back to reference Qin J, Yang B, Xu BQ, Smithc A, Xu L, Yuan JL, et al. Concurrent CD44s and STAT3 expression in human clear cell renal cellular carcinoma and its impact on survival. Int J Clin Exp Pathol. 2014;7:3235–44.PubMedPubMedCentral Qin J, Yang B, Xu BQ, Smithc A, Xu L, Yuan JL, et al. Concurrent CD44s and STAT3 expression in human clear cell renal cellular carcinoma and its impact on survival. Int J Clin Exp Pathol. 2014;7:3235–44.PubMedPubMedCentral
19.
go back to reference Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002;20:289–96.CrossRefPubMed Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002;20:289–96.CrossRefPubMed
20.
go back to reference Horiguchi A, Oya M, Shimada T, Uchida A, Marumo K, Murai M. Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome. J Urol. 2002;168:762–5.CrossRefPubMed Horiguchi A, Oya M, Shimada T, Uchida A, Marumo K, Murai M. Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome. J Urol. 2002;168:762–5.CrossRefPubMed
21.
go back to reference Tam L, McGlynn LM, Traynor P, Mukherjee R, Bartlett JM, Edwards J. Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer. Br J Cancer. 2007;97:378–83.CrossRefPubMedPubMedCentral Tam L, McGlynn LM, Traynor P, Mukherjee R, Bartlett JM, Edwards J. Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer. Br J Cancer. 2007;97:378–83.CrossRefPubMedPubMedCentral
26.
Metadata
Title
Association of Expression Levels or Activation Status of STAT3 with Treatment Outcomes of Sunitinib in Patients with Renal Cell Carcinoma
Authors
Kazuhiro Yamamoto
Takuto Hara
Tsutomu Nakagawa
Midori Hirai
Hideaki Miyake
Masato Fujisawa
Ikuko Yano
Publication date
01-06-2018
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 3/2018
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-018-0563-4

Other articles of this Issue 3/2018

Targeted Oncology 3/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine