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Colony-stimulating factors detected in tumor cells and voided urine are potential prognostic markers for patients with muscle-invasive bladder cancer undergoing radical cystectomy

Authors Morizawa Y, Miyake M, Shimada K, Hori S, Tatsumi Y, Nakai Y, Tanaka N, Fujii T, Fujimoto K

Received 24 February 2018

Accepted for publication 31 May 2018

Published 21 September 2018 Volume 2018:10 Pages 103—111

DOI https://doi.org/10.2147/RRU.S166497

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Jan Colli


Yosuke Morizawa,1 Makito Miyake,1 Keiji Shimada,2 Shunta Hori,1 Yoshihiro Tatsumi,1 Yasushi Nakai,1 Nobumichi Tanaka,1 Tomomi Fujii,3 Kiyohide Fujimoto1

1Department of Urology, Nara Medical University, Nara, Japan; 2Department of Pathology, Nara City Hospital, Nara, Japan; 3Department of Diagnostic Pathology, Nara Medical University, Nara, Japan

Background: The clinical use of macrophage colony-stimulating factor, granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) has improved the safety of cytotoxic chemotherapy. However, the overexpression of these CSFs in cancers has been reported to be associated with a poor prognosis in various malignancies. We evaluated the potential of CSF expression as a predictor of clinical outcome in patients with muscle-invasive bladder cancer (MIBC).
Methods: Consecutive patients (n=58) with MIBC who underwent radical cystectomy (RC) were included in this retrospective study. Treatment-naïve tumor specimens obtained by initial transurethral resection of bladder tumors prior to RC were immunostained with antibodies against macrophage colony-stimulating factor, G-CSF, and GM-CSF. We compared the clinicopathological variables and survival between these groups. Baseline levels of CSFs in the serum and voided urine were quantified using an enzyme-linked immunosorbent assay and compared with the expression of CSFs in the tumor lesions.
Results: Low expression of GM-CSF in the tumor cells was significantly correlated with a pathological T4 category (vs T2–3; P=0.02). In univariate survival analysis, high G-CSF and low GM-CSF expression in the tumor lesion were associated with poor outcomes. Furthermore, Cox proportional regression analysis revealed that high G-CSF and low GM-CSF expression in the tumor were independent predictors of shorter recurrence-free survival, cancer-specific survival, and overall survival. The levels of CSFs in voided urine were associated with the expression of CSFs in the tumor lesions.
Conclusion: GM-CSF and G-CSF expression in the tumor lesions obtained by initial transurethral resection are independent predictors of poor outcome in MIBC after RC. Levels of G-CSF and GM-CSF in urine before treatment could be useful in prognostication.

Keywords: colony-stimulating factor, M-CSF, G-CSF, GM-CSF, muscle-invasive bladder cancer, radical cystectomy

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