Background. To evaluate whether the overexpression of chemokine receptor-7 (CXCR7) in prostatic tissues obtained from men with Castration-Resistant Prostate Cancer (CRPC) is associated with resistance to enzalutamide (Enza). Methods. Based on the inclusion criteria of CRPC in EAU guidelines, all eligible patients treated in our hospital from January 2015 to December 2019 were included. Cases underwent radical prostatectomy, docetaxel-based chemotherapy, or new endocrine therapies (including Enza or abiraterone), and cases with severe cardiopulmonary disease or other malignant tumors were excluded. After immunohistochemical staining for CXCR7 expression in prostatic biopsy tissues, all enrolled cases were divided into two groups, namely, the CXCR7-positive group and the CXCR7-negative group. And then, PSA response to Enza treatment was recorded in detail and comparatively analyzed. In addition, the Cox proportional hazard modeling and the Kaplan-Meier analysis were used to determine PSA progression-free survival (PSAP-FS) and clinical or radiographic progression-free survival (CRP-FS) in this cohort. Results. A total of 79 CRPC individuals were enrolled and evaluated in this study. Median follow-up durations were 24 months (range, 12-42) in the CXCR7-positive group () and 28.5 months (range, 12-42) in the CXCR7-negative group (). The patients with lower CXCR7 expression showed much better PSA response to Enza treatment. There was 84.4% of CXCR7- cases showing decreasing PSA response, while there were 71.4% in the CXCR7/1+ group and 31.2% in the CXCR7/2+ group, respectively. All patients in the CXCR7/3+ group showed increasing PSA response to Enza treatment. And the percentage of patients whose PSA decreased over 50% is significantly higher in the CXCR7-negative group than in the CXCR7-positive group (68.8% vs. 8.5%, ), and the percentage of patients whose PSA decreased over 90% is also remarkably higher in the CXCR7-negative group (43.8% vs. 0, ). The Kaplan-Meier analysis demonstrated that the oncologic outcomes of CXCR7-negative patients were improved much significantly by Enza treatment in comparison with those of CXCR7-positive patients. Significantly increased median PSAP-FS (21 months vs. 6 months, ) and CRP-FS (27 months vs. 9 months, ) were obtained in the CXCR7-negative group. The further stratified analysis in all CXCR7-positive patients demonstrated that the patients with higher CXCR7 expression showed much worse outcome. The median time of PSAP-FS was 21 months in the CXCR7/1+ group, 9 months in the CXCR7/2+ group, and 6 months in the CXCR7/3+ group, while the median time of CRP-FS was 21 months in the CXCR7/1+ group, 12 months in the CXCR7/2+ group, and 6 months in the CXCR7/3+ group, respectively. Conclusion. Overexpression of CXCR7 induced by an AR antagonist in CRPC patients displays much better treatment response to Enza. CXCR7 might be a novel therapeutic target gene for CRPC patients.

中文翻译：

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CXCR7 的过表达是去势抵抗性前列腺癌患者恩杂鲁胺耐药的新指标

背景。评估从患有去势抵抗性前列腺癌 (CRPC) 的男性获得的前列腺组织中趋化因子受体 7 (CXCR7) 的过表达是否与对恩杂鲁胺 (Enza) 的耐药性相关。方法. 根据 EAU 指南中 CRPC 的纳入标准，纳入 2015 年 1 月至 2019 年 12 月在我院治疗的所有符合条件的患者。接受根治性前列腺切除术、以多西他赛为基础的化疗或新的内分泌治疗（包括恩扎或阿比特龙）的病例，排除严重心肺疾病或其他恶性肿瘤的病例。对前列腺活检组织中CXCR7表达进行免疫组化染色后，将所有入选病例分为两组，即CXCR7阳性组和CXCR7阴性组。然后，详细记录对 Enza 治疗的 PSA 反应并进行比较分析。此外，结果。本研究共招募和评估了 79 名 CRPC 个体。CXCR7 阳性组的中位随访时间为 24 个月（范围 12-42）（)和 28.5 个月 (范围, 12-42) 在 CXCR7 阴性组 (）。CXCR7 表达较低的患者对 Enza 治疗表现出更好的 PSA 反应。84.4% 的 CXCR7- 病例显示 PSA 反应降低，而 CXCR7/1+ 组和 CXCR7/2+ 组分别为 71.4% 和 31.2%。CXCR7/3+ 组中的所有患者都表现出对 Enza 治疗的 PSA 反应增加。并且 CXCR7 阴性组 PSA 下降超过 50% 的患者比例显着高于 CXCR7 阳性组（68.8% vs. 8.5%，),并且 PSA 下降超过 90% 的患者百分比在 CXCR7 阴性组中也明显更高 (43.8% vs. 0,）。Kaplan-Meier 分析表明，与 CXCR7 阳性患者相比，Enza 治疗显着改善了 CXCR7 阴性患者的肿瘤学结果。中位 PSAP-FS 显着增加（21 个月 vs. 6 个月，)和 CRP-FS（27 个月对 9 个月，)在 CXCR7 阴性组中获得。对所有 CXCR7 阳性患者的进一步分层分析表明，具有较高 CXCR7 表达的患者显示出更差的结果。CXCR7/1+组PSAP-FS的中位时间为21个月，CXCR7/2+组为9个月，CXCR7/3+组为6个月，而CRP-FS的中位时间为21个月CXCR7/1+组、CXCR7/2+组12个月、CXCR7/3+组6个月。结论。在 CRPC 患者中由 AR 拮抗剂诱导的 CXCR7 过表达显示出对 Enza 更好的治疗反应。CXCR7 可能是 CRPC 患者的新型治疗靶基因。