This study investigated the prognostic value of the chemokine C-C motif ligand 2 (CCL2) and its receptor C-C motif chemokine receptor 2 (CCR2) expression in locally advanced prostate cancer treated with radiotherapy and androgen deprivation using the 10-year outcome data from the TROG 03.04 RADAR clinical trial. CCL2 and CCR2 protein expression in prostate cancer biopsies at the time of diagnosis were quantified by immunohistochemistry and digital quantification. CCR2 protein expression was detected in prostate cancer cells and was associated with prostate-specific antigen serum concentration (p= 0.045). However, neither CCL2 nor CCR2 tissue expression could predict prostate cancer progression, or other clinicopathological parameters including perineural invasion and patient outcome. In serum samples, CCL2 concentration at the time of diagnosis, as assayed by enzyme-linked immunosorbent assay, was significantly higher in patients with prostate cancer compared with benign prostatic hyperplasia (median difference 0.22 ng/mL, 95% CI, 0.17–0.30) (p< 0.0001) and normal controls (median difference 0.13 ng/mL, 95% CI, 0.13–0.17) (p< 0.0001). However, circulating CCL2 was not statistically significant as a predictor of disease progression and patient outcome. In conclusion, this study shows that although CCL2 and CCR2 are expressed in prostate cancer, with an increased level of CCL2 in the serum, neither CCL2 nor CCR2 expression has a clinical prognostic value in locally advanced prostate cancer.
本研究利用TROG 03.04 RADAR临床试验的10年随访数据,探讨了趋化因子CC基序配体2(CCL2)及其受体CC基序趋化因子受体2(CCR2)在放疗联合雄激素剥夺治疗的局部晚期前列腺癌中的预后价值。通过免疫组织化学和数字化定量技术,对诊断时前列腺癌活检组织中的CCL2和CCR2蛋白表达进行量化分析。结果显示,CCR2蛋白在前列腺癌细胞中表达,且与前列腺特异性抗原血清浓度相关(p=0.045)。然而,无论是CCL2还是CCR2的组织表达均不能预测前列腺癌进展,亦无法预测包括神经周围侵犯在内的其他临床病理参数及患者预后。在血清样本中,通过酶联免疫吸附测定发现,诊断时前列腺癌患者的CCL2浓度显著高于良性前列腺增生患者(中位数差值0.22 ng/mL,95% CI 0.17-0.30)(p<0.0001)和正常对照组(中位数差值0.13 ng/mL,95% CI 0.13-0.17)(p<0.0001)。但循环CCL2作为疾病进展和患者预后的预测指标无统计学意义。综上所述,本研究显示尽管CCL2和CCR2在前列腺癌中表达且血清CCL2水平升高,但二者在局部晚期前列腺癌中均不具备临床预后价值。