前列腺特异性抗原同源异构体2及其衍生指标在预测前列腺癌病理分级中的价值

目的 探讨血清前列腺特异性抗原同源异构体2(isoform [-2] proprostate-specific antigen,p2PSA)及经计算得到的%p2PSA和前列腺健康指数(prostate health index,PHI)等指标预测前列腺癌(prostate cancer, PCa)病理分级的价值.方法: 回顾性入组了322例来自北京大学第一医院在2015年8月至2018年5月期间就诊的PCa患者,其中143例为进行经直肠超声引导的前列腺穿刺活检证实的PCa患者,179例为进行PCa根治术的患者.采用全自动免疫分析仪DxI800检测患者的术前预留血清中前列腺特异性抗原(total prostate-specific antigen,tPSA),游离前列腺抗原(free prostate antigen,fPSA),fPSA/tPSA比值(f/t),p2PSA水平,并计算得到%p2PSA 和PHI,以术后病理结果确定Gleason评分,采用受试者工作曲线(receiver operating characteristic curve,ROC)比较p2PSA,%p2PSA及PHI与传统指标tPSA,fPSA和f/t预测高级别前列腺癌(Gleason评分≥7)的价值.结果: Gleason评分≥7患者的p2PSA,%p2PSA和 PHI的中位数水平均高于Gleason评分<7患者(p2PSA: 30.22 ng/L vs. 18.33 ng/L; %p2PSA: 2.50 vs. 1.27; PHI: 91.81 vs. 35.44; P值均<0.01).%p2PSA和PHI预测高级别PCa的曲线下面积(area under curve,AUC)为0.770和0.760,高于传统指标tPSA,fPSA和f/t(AUC分别为0.648,0.536和 0.693).进行前列腺穿刺术证实为PCa的患者中,PHI和%p2PSA预测高级别PCa的价值(AUC分别为0.801和0.808)明显高于tPSA,fPSA和f/t(AUC分别为0.729,0.655和0.665).进行PCa根治术后的患者中,PHI 和%p2PSA预测高级别PCa的价值(AUC分别为 0.798和0.744)也有高于其他传统指标tPSA,fPSA和f/t (AUC分别为0.625, 0.507和0.697)的趋势.结论: 与传统指标tPSA,fPSA和f/t相比,p2PSA的衍生指标%p2PSA和PHI对于高级别PCa具有更高的预测价值,可以帮助临床评估PCa治疗方案,为患者及时制定更合适的诊疗策略.

Clinical value of serum isoform [-2] proprostate-specific antigen and its derivatives in predicting aggressive prostate cancer

Objective: To explore the clinical value of serum isoform [-2] proprostate-specific antigen (p2PSA) and its derivatives %p2PSA and prostate health index (PHI) in predicting aggressive prostate cancer (PCa).Methods: The pre-operation serum and basic clinical data of 322 patients with PCa (including 143 patients diagnosed with PCa by transrectal ultrasound-guided prostate biopsy and 179 patients undergoing radical prostatectomy) in Peking University First Hospital were collected from August 2015 to May 2018. Serum total prostate-specific antigen (tPSA), free prostate antigen (fPSA) and fPSA/tPSA (f/t) and the p2PSA level of all these patients were measured on automatic immune analyzers DxI800, and then %p2PSA and PHI were calculated. The prostate pathologic result was considered as the gold standard to evaluate the Gleason score of the patients with PCa. Receiver operator curves (ROC) were used to assess the ability of p2PSA, %p2PSA and PHI to predict aggressive PCa (pathologic Gleason score≥7) compared with those traditional markers tPSA, fPSA and f/t.Results: Among these patients, the p2PSA, %p2PSA and PHI median levels were significantly higher in patients with pathologic Gleason score≥7 than those with Gleason score<7 (p2PSA: 30.22 ng/L vs. 18.33 ng/L; %p2PSA: 2.50 vs. 1.27; PHI:91.81 vs. 35.44;all P<0.01). The area under curve (AUC) of %p2PSA and PHI (0.770, 0.760) in predicting Gleason score≥7 were higher than those of the traditional indicators tPSA, fPSA and f/t (AUC were 0.648, 0.536 and 0.693, respectively). Among those patients diagnosed with PCa by transrectal ultrasound-guided prostate biopsy, the AUC of %p2PSA and PHI (AUC were 0.808 and 0.801, respectively) in predicting Gleason score≥7 were higher than those of the traditional indicators tPSA, fPSA and f/t (AUC were 0.729,0.655 and 0.665 respectively). Among those patients undergoing radical prostatectomy, PHI and %p2PSA also had the trend of higher predictive value than those of the traditional indicators. The AUC of %p2PSA and PHI were 0.798 and 0.744, respectively while the AUC of tPSA, fPSA and f/t were 0.625, 0.507 and 0.697, respectively.Conclusion: Compared with traditional markers tPSA, fPSA and f/t, %p2PSA and PHI had much higher predictive value for aggressive PCa, which may help clinicians to evaluate the therapeutic regime and make more appropriate management plan for the patients.