目的 探讨醋酸阿比特龙联合多西他赛与泼尼松在转移性去势抵抗性前列腺癌（mCRPC）患者中的应用及N-末端α位乙酰基转移酶基因10（acetyltransferase gene 10，Naa10）与治疗敏感性的关系。方法 回顾性选择2017年10月-2019年12月邢台医学高等专科学校第二附属医院收治的122例mCRPC患者为研究对象，入选患者均经过雄激素剥夺治疗。根据治疗方案不同将患者分为对照组和试验组，对照组患者静脉滴注多西他赛注射液，剂量75 mg·m^-2，每3周1次；口服醋酸泼尼松片，1次1片，每天2次；在注射多西他赛注射液化疗前1天、当天和后1天均口服醋酸地塞米松片，1日2次，总剂量7.5 mg。试验组患者在对照组的基础上空腹口服醋酸阿比特龙片，每次1 g，每日1次，治疗4个周期（12周）。比较两组患者近期临床疗效、不良反应及远期生存率等情况，随访3年，计算患者的中位生存期。免疫组化法检测mCRPC癌组织中Naa10蛋白表达，将患者分成Naa10阳性表达组和阴性表达组，分析其临床病理参数，单因素和Cox回归分析确定影响mCRPC预后的因素，分析Naa10蛋白阳性表达与治疗敏感性的关系。结果 治疗4个周期后，试验组患者9例完全缓解、40例部分缓解、8例疾病稳定及4例疾病进展，治疗总有效率为80.33%；对照组患者2例完全缓解、34例部分缓解、20例疾病稳定及5例疾病进展，治疗总有效率为59.02%，两组间比较差异显著（χ²=6.556，P=0.011）。试验组和对照组患者均出现骨髓抑制（χ²=0.209，P=0.648）、肝功能损伤（χ²=0.830，P=0.362）、胃肠道反应（χ²=0.370，P=0.543）、水钠潴留（χ²=0.209，P=0.648）及心脏毒性（χ²=0.899，P=0.343）等3级以上不良反应，但两组间差异未见显著性。mCRPC癌组织中Naa10蛋白阳性表达与治疗周期（χ²=9.106，P=0.003）、淋巴结转移（χ²=5.055，P=0.025）、T分期（χ²=4.391，P=0.036）、骨转移病灶数（χ²=19.863，P=0.000）、内脏转移（χ²=5.009，P=0.025）等具有显著相关性，但与年龄（χ²=3.059，P=0.080）、化疗方案（χ²=0.880，P=0.348）、EOCG评分（χ²=3.453，P=0.178）、民族（χ²=0.135，P=0.713）及Gleason评分（χ²=0.837，P=0.360）等没有显著相关性。单因素分析结果显示，mCRPC患者中位生存期与EOCG评分（χ²=7.464，P=0.006）、淋巴结转移（χ²=6.114，P=0.013）、化疗方案（χ²=7.049，P=0.030）、治疗周期（χ²=5.051，P=0.038）、T分期（χ²=1.196，P=0.035）、骨转移病灶数（χ²=9.611，P=0.008）、内脏转移（χ²=1.085，P=0.048）及Naa10蛋白阳性表达（χ²=15.600，P=0.000）等指标具有显著相关性。Cox回归分析结果显示，骨转移病灶数（>10个）（OR=2.404，95% CI：1.424~4.056）、治疗周期（>8个疗程）（OR=0.458，95% CI：0.253~0.832）、化疗方案（试验组）（OR=0.360，95% CI：0.160~0.801）和Naa10蛋白阳性表达（OR=2.563，95% CI：2.106~3.117）是mCRPC患者预后生存的独立影响因素（P<0.05）。结论 醋酸阿比特龙联合多西他赛与泼尼松应用于mCRPC治疗，可有效提高近期临床疗效，延长生存期，且不增加不良反应，同时Naa10蛋白高表达是mCRPC患者预后不良的危险因素，临床宜监测指标，及时调整和评估临床治疗效果。

Objective To study the abiraterone acetate combined with docetaxel and prednisone in mCRPC patients and the relationship between Naa10 and treatment sensitivity. Methods A total of 122 patients with mCRPC admitted to The Second Affiliated Hospital of Xingtai Medical College from October 2017 to December 2019 were selected and treated with androgen deprivation therapy, the patients were divided into the control group and the experiment group according to different treatment schemes. The patients in the control group were given Docetaxel Injection intravenously at a dose of 75 mg·m^-2 once every three weeks. Oral prednisone acetate tablets, once, twice a day. Dexamethasone Acetate Tablets were taken orally one day before, one day after and one day after the injection of Docetaxel Injection chemotherapy, twice a day, with a total dose of 7.5 mg. On the basis of the control group, the patients in the experimental group took Abiraterone Acetate Tablets orally on an empty stomach, 1 g each time, once a day, for four cycles (12 weeks). The short-term clinical efficacy, adverse reactions and long-term survival rate of the two groups were compared. The patients were followed up for three years to calculate the median survival time. The expression of Naa10 protein in mCRPC cancer tissues was detected by immunohistochemistry. The patients were divided into Naa10 positive expression group and negative expression group. The clinicopathological parameters were analyzed. The factors affecting the prognosis of mCRPC were determined by univariate and Cox regression analysis, and the relationship between Naa10 protein positive expression and treatment sensitivity was analyzed. Results After four cycles of treatment, nine patients in the experimental group had complete remission, 40 patients had partial remission, eight patients had stable disease and four patients had disease progression. The total effective rate was 80.33%. In the control group, there were two cases of complete remission, 34 cases of partial remission, 20 cases of disease stability and five cases of disease progression. The total effective rate was 59.02%. There was significant difference between the two groups (χ²=6.556, P=0.011). Bone marrow suppression (χ²=0.209, P=0.648), liver function damage (χ²=0.830, P=0.362), gastrointestinal reaction (χ²=0.370, P=0.543), water and sodium retention (χ²=0.209, P=0.648) and cardiac toxicity (χ²=0.899, P=0.343) occurred in both the experimental group and the control group, but no significant difference was found. The positive expression of Naa10 protein in mCRPC cancer tissue was correlated with the treatment period (χ²=9.106, P=0.003), lymph node metastasis (χ²=5.055, P=0.025), T stage (χ²=4.391, P=0.036), the number of bone metastases (χ²=19.863, P=0.000), and visceral metastases (χ²=5.009, P=0.025). But not with age (χ²=3.059, P=0.080), chemotherapy (χ²=0.880, P=0.348), EOCG score (χ²=3.453, P=0.178), the national (χ²=0.135, P=0.713) and Gleason score (χ²=0.837, P=0.360). Univariate analysis showed that median survival time of mCRPC patients was correlated with EOCG score (χ²=7.464, P=0.006), lymph node metastasis (χ²=6.114, P=0.013), chemotherapy regimen (χ²=7.049, P=0.030), treatment cycle (χ²=5.051, P=0.038), T stage (χ²=1.196, P=0.035), the number of bone metastases lesions (χ²=9.611, i=0.008), internal transfer (χ²=1.085, P=0.048) and Naa10 protein expression (χ²=15.600, P=0.000) were statistically significant. Cox regression analysis showed that the number of bone metastases (> 10) (OR=2.404, 95%CI:1.424-4.056), treatment cycle (> 8 courses) (OR=0.458, 95%CI:0.253- 0.832), chemotherapy regimen (experiment group) (OR=0.360, 95%CI:0.160-0.801) and Naa10 protein positive expression (OR=2.563, 95%CI:2.106-3.117) were independent factors affecting the survival of mCRPC patients (P < 0.05). Conclusion Abiraterone acetate combined with docetaxel and prednisone can effectively improve the short-term clinical efficacy and prolong survival without increasing adverse reactions in mCRPC patients. Meanwhile, high expression of Naa10 protein is a risk factor for poor prognosis in mCRPC patients. Therefore, it is advisable to monitor indicators and timely adjust and evaluate the clinical treatment effect, which is worthy of clinical research.

R979.1

邢台市重点研发计划项目（2020ZC328）