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

Abstract

BackgroundThe 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).MethodsConsecutive 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.ResultsLow 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.ConclusionGM-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.

Tumor-Associated Macrophages in Bladder Cancer: Biological Role, Impact on Therapeutic Response and Perspectives for Immunotherapy

“…Even if CSF1 was secreted by bladder tumor cells [ 162 , 163 ], only 34% of patients have a high expression of CSF1 in tumor tissues. Moreover, CSF1 expression was neither associated with clinicopathological features nor correlated with RFS or CSS [ 164 ]. However, CSF1 serum and urine levels of MIBC patients were higher than those of NMIBC patients and controls [ 164 ].…”

“…Moreover, CSF1 expression was neither associated with clinicopathological features nor correlated with RFS or CSS [ 164 ]. However, CSF1 serum and urine levels of MIBC patients were higher than those of NMIBC patients and controls [ 164 ].…”

BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer

“…The delivered cargo system induces its immune response through stimulation of GM-CSF in Rb protein-deficient cells. GM-CSF expression typically leads to downstream granulocyte, macrophage, lymphocyte, and dendritic cell activation, which has been implicated in antitumor activity in many malignancies [82][83][84].…”

Clinical Impact of Tumor-Infiltrating Lymphocytes and PD-L1-Positive Cells as Prognostic and Predictive Biomarkers in Urological Malignancies and Retroperitoneal Sarcoma

“…Figure 2 shows representative images of IHC staining of seven immune-related markers using surgically resected UC specimens. Our previous works have presented the oncogenic or anti-tumoral effect of endogenous and exogenous colony-stimulating factors (CSFs) in UC [80][81][82]. In addition, accumulating evidence revealed that CD204, but not CD163, positive tumor-associated macrophages are associated with the aggressive behavior of various cancers including UC [16,83].…”