摘要
目的探讨超声引导下前列腺穿刺联合外周血循环肿瘤细胞(CTCs)检测对前列腺癌预后的预测效果。方法选取2011年1月至2017年12月期间于郑州大学第二附属医院收治的83例前列腺癌患者为研究对象,全部患者均根据超声引导下经直肠前列腺穿刺活检术确诊为前列腺癌,检测病理标本中CK34BE12、p63、α-甲酰基辅酶A消旋酶(AMACR)等免疫标志物的表达状况,并采用Cell Search细胞搜索系统检测外周血CTCs的数量,据此分为阳性组(≥5个/7.5 ml)和阴性组(<5个/7.5 ml)。分析穿刺组织中免疫标志物表达状况、外周血CTCs计数与患者临床病理特征、生存状况的相关性。各标志物的阳性例数、Gleason评分>7分的比例、TNM分期等定性资料的比较采用x^2检验或Fisher确切概率法,年龄、血常规、凝血功能、肝功能、PSA水平等定量资料的比较采用t检验。采用Kaplan-Meier法进行生存分析,采用多因素Cox比例风险回归模型分析患者预后的预测因素。结果(1)全部患者中外周血CTCs、穿刺组织中CK34BE12、p63、AMACR的阳性率分别为31.33、3.61、3.61、86.75。CTCs阳性组的AMACR阳性率为100.00,高于CTCs阴性组的80.70,差异有统计学意义(x^2=4.227,P<0.05)。(2)AMACR阳性组患者的血红蛋白(HB)低于AMACR阴性组[(123.66±13.33)g/L比(134.89±20.08)g/L,t=2.420,P=0.018],血小板(PLT)、血清谷丙转氨酶、D-二聚体(DD)、前列腺特异抗原(PSA)水平、Gleason评分>7分的比例均高于AMACR阴性组[(197.23±36.98)×10^9/L比(172.83±33.33)×10^9/L,t=2.062,P=0.042;(38.80±10.03)U/L比(31.46±7.83)U/L,t=2.317,P=0.023;(255.00±38.80)μg/L比(220.81±30.99)μg/L,t=2.785,P=0.007;(26.60±12.23)ng/ml比(17.90±8.88)ng/ml,t=2.263,P=0.026;45.83比9.09,x^2=3.916,P=0.048],差异有统计学意义(P<0.05)。CTCs阳性组患者的HB低于CTCs阴性组[(121.69±15.89)g/L比(132.73±18.85)g/L,t=2.767,P=0.007],血清碱性磷酸酶、DD、PSA水平、Gleason评分>7分、T3~T4期、M1期的比例均高于CTCs阴性组[(105.69±30.56)U/L比(88.89±35.58)U/L,t=2.205,P=0.030;(256.63±35.86)μg/L比(236.98±33.30)μg/L,t=2.368,P=0.020;(30.09±11.89)ng/ml比(23.33±10.99)ng/ml,t=2.533,P=0.013;57.69比33.33,x^2=4.381,P=0.036;30.77比8.77,x^2=4.981,P=0.026;50.00比17.54,x^2=9.390,P=0.002],差异有统计学意义(P<0.05)。(3)全部患者的中位生存时间为58.33个月,1、3、5年的生存率分别为88.95、51.81、30.12。AMACR阳性组、CTCs阳性组患者的中位生存时间为40.93、36.93个月,低于AMACR阴性组、CTCs阴性组的66.66、69.56个月,差异有统计学意义(P<0.05)。多因素Cox比例风险回归模型分析结果表明,Gleason评分>7分、M1期、AMACR阳性、CTCs阳性是患者死亡的独立危险因素(HR=1.883、3.666、2.009、2.923,P<0.05)。结论超声引导下前列腺穿刺联合外周血CTCs检测对前列腺癌患者的预后具有重要的预测价值,临床上可根据穿刺组织中AMACR表达水平和外周血CTCs计数进行预后的综合分析。
Objective To investigate the prediction effect of ultrasound-guided prostate puncture combined with circulation tumor cells(CTCs)enumeration on prognosis of prostate cancer.Methods 83 patients with prostate cancer admitted to our hospital from January 2011 to December 2017 were enrolled for the study.All patients were diagnosed as prostate cancer by ultrasound-guided transrectal prostate biopsy,and the expression of immune markers including CK34BE12,p63 andα-methylacyl CoA racemase(AMACR)in pathological specimens were detected.Cell Search system was performed to detect the number of CTCs in peripheral blood,which was divided into positive group(>5/7.5 ml)and negative group(<5/7.5 ml).The correlations of the expression of immune markers in biopsy tissues,the number of CTCs in peripheral blood and the clinicopathological features and survival status of patients were analyzed.The number of positive cases of each marker,the proportion of Gleason score>7 points,TNM stage and other qualitative data were compared by x^2 test,and the quantitative data such as age,blood routine test,coagulation function,liver function and PSA level were compared by t test.Kaplan Meier method was used for survival analysis,and multivariate Cox proportional risk regression model was used to analyze the prognostic factors.Results(1)The positive rates of CTCs in peripheral blood,CK34BE12,p63 and AMACR in biopsy tissues were 31.33,3.61,3.61 and 86.75 respectively.The positive rate of AMACR in CTCs positive group was 100.00,and significantly higher than 80.70 in CTCs negative group(x^2=4.227,P<0.05).(2)Hemoglobin(HB)of AMACR positive group was significantly lower than that in AMACR negative group[(123.66±13.33)g/L vs(134.89±20.08)g/L,t=2.420,P=0.018].Platelet(PLT),serum levels of alanine aminotransferase,D-dimer(DD),prostate specific antigen(PSA)and proportion of Gleason score>7 in AMACR positive group were significantly higher than those in AMACR negative group[(197.23±36.98)×10^9/L vs(172.83±33.33)×10^9/L,t=2.062,P=0.042;(38.80±10.03)U/L vs(31.46±7.83)U/L,t=2.317,P=0.023;(255.00±38.80)μg/L vs(220.81±30.99)μg/L,t=2.785,P=0.007;(26.60±12.23)ng/ml vs(17.90±8.88)ng/ml,t=2.263,P=0.026;45.83 vs 9.09,c2=3.916,P=0.048].HB of CTCs positive group was significantly lower than that of CTCs negative group[(121.69±15.89)g/L vs(132.73±18.85)g/L,t=2.767,P=0.007].Serum levels of alkaline phosphatase,DD,PSA,proportions of Gleason score>7,T3-T4 stage and M1 stage in CTCs positive group were significantly higher than those in CTCs negative group[(105.69±30.56)U/L vs(88.89±35.58)U/L,t=2.205,P=0.030;(256.63±35.86)μg/L vs(236.98±33.30)μg/L,t=2.368,P=0.020;(30.09±11.89)ng/ml vs(23.33±10.99)ng/ml,t=2.533,P=0.013;57.69 vs 33.33,c2=4.381,P=0.036;30.77 vs 8.77,c2=4.981,P=0.026;50.00 vs 17.54,c2=9.390,P=0.002].(3)The median survival time of all patients was 58.33 months,and the 1,3 and 5-year survival rates were 88.95,51.81 and 30.12 respectively.The median survival time of AMACR positive group and CTCs positive group were 40.93 and 36.93 months,which were significantly lower than 66.66 and 69.56 months of AMACR negative group and CTCs negative group respectively(P<0.05).(4)Multivariate Cox proportional regression analysis showed that Gleason score>7,M1 stage,AMACR positive and CTCs positive were the independent risk factors for death(HR=1.883,3.666,2.009,2.923,P<0.05).Conclusions Ultrasound-guided prostate puncture combined with CTCs enumeration in peripheral blood exert important predictive value for the prognosis of prostate cancer patients,and the prognosis could be comprehensively analyzed according to AMACR expression level in biopsy tissue and CTCs count in peripheral blood.
作者
王志国
王友志
许长宝
刘昌伟
郝斌
Wang Zhiguo;Wang Youzhi;Xu Changbao;Liu Changwei;Hao bin(the Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450013,China)
出处
《中华细胞与干细胞杂志（电子版）》
2019年第6期327-332,共6页
Chinese Journal of Cell and Stem Cell（Electronic Edition）
