Marsland Mark, Jiang Chen Chen, Faulkner Sam, Steigler Allison, McEwan Kristen, Jobling Phillip, Oldmeadow Christopher, Delahunt Brett, Denham James W, Hondermarck Hubert
School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW 2305, Australia.
Cancers (Basel). 2024 Aug 8;16(16):2794. doi: 10.3390/cancers16162794.
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 ( = 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) ( < 0.0001) and normal controls (median difference 0.13 ng/mL, 95% CI, 0.13-0.17) ( < 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，探讨趋化因子C-C基序配体2（CCL2）及其受体C-C基序趋化因子受体2（CCR2）的表达在接受放疗和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定量法对诊断时前列腺癌活检组织中CCL2和CCR2蛋白表达进行定量。在前列腺癌细胞中检测到CCR2蛋白表达，且其与前列腺特异性抗原血清浓度相关（P = 0.045）。然而，CCL2和CCR2的组织表达均无法预测前列腺癌进展或其他临床病理参数，包括神经周围浸润和患者预后。在血清样本中，通过酶联免疫吸附测定法检测发现，前列腺癌患者诊断时的CCL2浓度显著高于良性前列腺增生患者（中位数差异为0.22 ng/mL，95%可信区间为0.17 - 0.30）（P < 0.0001）和正常对照（中位数差异为0.13 ng/mL，95%可信区间为0.13 - 0.17）（P < 0.0001）。然而，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。总之，本研究表明，尽管CCL2和CCR2在前列腺癌中表达，且血清中CCL2水平升高，但CCL2和CCR2的表达在局部晚期前列腺癌中均无临床预后价值。
