目的 探討醋酸阿比特龍聯(lián)合多西他賽與潑尼松在轉(zhuǎn)移性去勢(shì)抵抗性前列腺癌（mCRPC）患者中的應(yīng)用及N-末端α位乙?；D(zhuǎn)移酶基因10（acetyltransferase gene 10，Naa10）與治療敏感性的關(guān)系。方法 回顧性選擇2017年10月-2019年12月邢臺(tái)醫(yī)學(xué)高等專(zhuān)科學(xué)校第二附屬醫(yī)院收治的122例mCRPC患者為研究對(duì)象，入選患者均經(jīng)過(guò)雄激素剝奪治療。根據(jù)治療方案不同將患者分為對(duì)照組和試驗(yàn)組，對(duì)照組患者靜脈滴注多西他賽注射液，劑量75 mg·m^-2，每3周1次；口服醋酸潑尼松片，1次1片，每天2次；在注射多西他賽注射液化療前1天、當(dāng)天和后1天均口服醋酸地塞米松片，1日2次，總劑量7.5 mg。試驗(yàn)組患者在對(duì)照組的基礎(chǔ)上空腹口服醋酸阿比特龍片，每次1 g，每日1次，治療4個(gè)周期（12周）。比較兩組患者近期臨床療效、不良反應(yīng)及遠(yuǎn)期生存率等情況，隨訪3年，計(jì)算患者的中位生存期。免疫組化法檢測(cè)mCRPC癌組織中Naa10蛋白表達(dá)，將患者分成Naa10陽(yáng)性表達(dá)組和陰性表達(dá)組，分析其臨床病理參數(shù)，單因素和Cox回歸分析確定影響mCRPC預(yù)后的因素，分析Naa10蛋白陽(yáng)性表達(dá)與治療敏感性的關(guān)系。結(jié)果 治療4個(gè)周期后，試驗(yàn)組患者9例完全緩解、40例部分緩解、8例疾病穩(wěn)定及4例疾病進(jìn)展，治療總有效率為80.33%；對(duì)照組患者2例完全緩解、34例部分緩解、20例疾病穩(wěn)定及5例疾病進(jìn)展，治療總有效率為59.02%，兩組間比較差異顯著（χ²=6.556，P=0.011）。試驗(yàn)組和對(duì)照組患者均出現(xiàn)骨髓抑制（χ²=0.209，P=0.648）、肝功能損傷（χ²=0.830，P=0.362）、胃腸道反應(yīng)（χ²=0.370，P=0.543）、水鈉潴留（χ²=0.209，P=0.648）及心臟毒性（χ²=0.899，P=0.343）等3級(jí)以上不良反應(yīng)，但兩組間差異未見(jiàn)顯著性。mCRPC癌組織中Naa10蛋白陽(yáng)性表達(dá)與治療周期（χ²=9.106，P=0.003）、淋巴結(jié)轉(zhuǎn)移（χ²=5.055，P=0.025）、T分期（χ²=4.391，P=0.036）、骨轉(zhuǎn)移病灶數(shù)（χ²=19.863，P=0.000）、內(nèi)臟轉(zhuǎn)移（χ²=5.009，P=0.025）等具有顯著相關(guān)性，但與年齡（χ²=3.059，P=0.080）、化療方案（χ²=0.880，P=0.348）、EOCG評(píng)分（χ²=3.453，P=0.178）、民族（χ²=0.135，P=0.713）及Gleason評(píng)分（χ²=0.837，P=0.360）等沒(méi)有顯著相關(guān)性。單因素分析結(jié)果顯示，mCRPC患者中位生存期與EOCG評(píng)分（χ²=7.464，P=0.006）、淋巴結(jié)轉(zhuǎn)移（χ²=6.114，P=0.013）、化療方案（χ²=7.049，P=0.030）、治療周期（χ²=5.051，P=0.038）、T分期（χ²=1.196，P=0.035）、骨轉(zhuǎn)移病灶數(shù)（χ²=9.611，P=0.008）、內(nèi)臟轉(zhuǎn)移（χ²=1.085，P=0.048）及Naa10蛋白陽(yáng)性表達(dá)（χ²=15.600，P=0.000）等指標(biāo)具有顯著相關(guān)性。Cox回歸分析結(jié)果顯示，骨轉(zhuǎn)移病灶數(shù)（>10個(gè)）（OR=2.404，95% CI：1.424~4.056）、治療周期（>8個(gè)療程）（OR=0.458，95% CI：0.253~0.832）、化療方案（試驗(yàn)組）（OR=0.360，95% CI：0.160~0.801）和Naa10蛋白陽(yáng)性表達(dá)（OR=2.563，95% CI：2.106~3.117）是mCRPC患者預(yù)后生存的獨(dú)立影響因素（P<0.05）。結(jié)論 醋酸阿比特龍聯(lián)合多西他賽與潑尼松應(yīng)用于mCRPC治療，可有效提高近期臨床療效，延長(zhǎng)生存期，且不增加不良反應(yīng)，同時(shí)Naa10蛋白高表達(dá)是mCRPC患者預(yù)后不良的危險(xiǎn)因素，臨床宜監(jiān)測(cè)指標(biāo)，及時(shí)調(diào)整和評(píng)估臨床治療效果。

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

邢臺(tái)市重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2020ZC328）