北京大学学报(医学版) ›› 2020, Vol. 52 ›› Issue (2): 234-239. doi: 10.19723/j.issn.1671-167X.2020.02.007

• 论著 • 上一篇    下一篇

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

孙奎霞,闫存玲(),李志艳,刘平,张伟,何群   

  1. 北京大学第一医院检验科,北京 100034
  • 收稿日期:2019-12-02 出版日期:2020-04-18 发布日期:2020-04-18
  • 通讯作者: 闫存玲 E-mail:yancunling@163.com

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

Kui-xia SUN,Cun-ling YAN(),Zhi-yan LI,Ping LIU,Wei ZHANG,Qun HE   

  1. Department of Clinical Laboratory, Peking University First Hospital, Beijing 100034, China
  • Received:2019-12-02 Online:2020-04-18 Published:2020-04-18
  • Contact: Cun-ling YAN E-mail:yancunling@163.com

摘要:

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.

关键词: 前列腺特异性抗原同源异构体2, 前列腺健康指数, 前列腺癌

Abstract:

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.

Key words: Isoform [-2] proprostate-specific antigen, Prostate health index, Prostate cancer

中图分类号: 

  • R737.2

表1

不同病理分级的前列腺癌人群基本资料和血清检测结果"

Items Gleason score≥7(n=278) Gleason score<7(n=44) t/U P
Age/years, $\bar{x}±s$ 67.5±7.1 67.8±7.9 0.238 >0.05
tPSA /(μg/L), M(Min, Max) 13.35 (0.03, 699.5) 8.11 (0.67, 57.33) 2.950 <0.01
fPSA/(μg/L), M(Min, Max) 1.29 (0.01, 47.84) 1.06 (0.26, 6.10) 0.714 >0.05
f/t, M(Min, Max) 0.10 (0.03, 0.67) 0.17(0.04, 0.42) 3.824 <0.01
p2PSA/(ng/L), M(Min, Max) 30.22 (0.25, 10254.36) 18.33 (3.94, 197.42) 3.516 <0.01
%p2PSA, M(Min, Max) 2.50 (0.08, 24.32) 1.27 (0.34, 6.04) 5.346 <0.01
PHI, M(Min, Max) 91.81 (0.01, 3037.97) 35.44 (8.95, 332.87) 5.038 <0.01

表2

总人群中各指标预测Gleason 评分≥7的前列腺癌的效能"

Items Cut-off value AUC 95%CI Sensitivity/% Specificity/%
tPSA/(μg/L) 9.76 0.648 0.592 - 0.701 63.8 67.6
fPSA/(μg/L) 1.25 0.536 0.476 - 0.589 50.3 58.9
f/t 0.16 0.693 0.639 - 0.744 73.1 51.4
p2PSA/(ng/L) 29.39 0.673 0.618 - 0.725 67.2 72.9
%p2PSA 1.68 0.770 0.719 - 0.815 83.3 74.9
PHI 64.00 0.760 0.709 - 0.806 81.1 78.4

图1

总体分析各指标预测前列腺癌患者的Gleason 评分≥7的ROC曲线"

表3

各指标预测Gleason 评分≥7的前列腺癌的效能(前列腺穿刺活检患者)"

Items Cut-off value AUC 95%CI Sensitivity/% Specificity/%
tPSA/ (μg/L) 9.76 0.729 0.647 - 0.801 76.8 66.7
fPSA/ (μg/L) 3.27 0.655 0.570 - 0.734 50.7 72.6
f/t 0.13 0.665 0.580 - 0.743 67.6 66.7
p2PSA/ (ng/L) 35.60 0.751 0.670 - 0.820 77.7 75.2
%p2PSA 1.87 0.808 0.732 - 0.870 80.5 74.1
PHI 54.90 0.801 0.725 - 0.864 80.2 77.8

图2

各指标预测前列腺穿刺活检确诊为前列腺癌患者的Gleason 评分≥7的ROC曲线"

表4

各指标预测Gleason 评分≥7的前列腺癌的效能(前列腺根治术患者)"

Items Cut-off value AUC 95%CI Sensitivity/% Specificity/%
tPSA/(μg/L) 8.51 0.625 0.549 - 0.696 61.7 70.0
fPSA/(μg/L) 0.95 0.507 0.431- 0.583 63.3 60.1
f/t 0.20 0.697 0.623 - 0.763 74.0 50.0
p2PSA/(ng/L) 23.95 0.710 0.637- 0.776 77.3 70.4
%p2PSA 1.52 0.744 0.673 - 0.806 84.6 69.7
PHI 35.44 0.798 0.731- 0.855 82.8 70.8

图3

各指标预测进行前列腺癌根治术患者的Gleason 评分≥7的ROC曲线"

[1] Stephan C, Vincendeau S, Houlgatte A , et al. Multicenter evaluation of [-2]proprostate-specific antigen and the prostate health index for detecting prostate cancer[J]. Clin Chem, 2013,59(1):306-314.
[2] 黄宜, 王文涓, 许静 , 等. p2PSA及其相关指标 PHI 在前列腺癌诊断中的应用价值[J]. 检验医学, 2019,34(7):600-604.
[3] Quinn D, Gross M . Show us a sign: the search for "game changing" prostate cancer biomarkers[J]. Lancet Oncol, 2011,12(3):204-206.
[4] Vukovic I, Djordjevic D, Bojanic N , et al. Predictive value of [-2]propsa(p2psa) and its derivatives for the prostate cancer detection in the 2.0 to 10.0 ng/mL PSA range[J]. Int Braz J Urol, 2017,43(1):48-56.
[5] 朱耀, 唐钵, 戴波 , 等. 前列腺健康指数在中国男性前列腺癌诊断中的应用研究[J]. 中华外科杂志, 2017,55(10):734-737.
[6] 闫存玲, 李志艳, 何群 , 等. 血清前列腺特异性抗原同源异构体-2在前列腺癌中的应用价值[J]. 中华检验医学杂志, 2015,38(12):813-817.
[7] Catalona WJ, Partin AW, Sanda MG , et al. A multicenter study of [-2]pro-prostate specific antigen combined with prostate speci-fic antigen and free prostate specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/ml prostate specific antigen range[J]. J Urol, 2011,185(5):1650-1655.
[8] Jansen FH, van Schaik RHN, Kurstjens J , et al. Prostate-specific antigen (PSA) isoform p2PSA in combination with total PSA and free PSA improves diagnostic accuracy in prostate cancer detection[J]. Eur Urol, 2010,57(6):921-927
[9] Fossati N, Buffi NM, Haese A , et al. Preoperative prostate speci-fic antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer: results from a multicentric European prospective study[J]. Eur Urol, 2015,68(1):132-138
[10] Eminaga O, Bögemann M, Breil B , et al. Preoperative prostate-specific antigen isoform p2PSA ≤ 22.5 pg/ml predicts advanced prostate cancer in patients undergoing radical prostatectomy[J]. Urol Oncol, 2014,32(8):1117-1126.
[11] Guazzoni G, Lazzeri M, Nava L , et al. Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radicalprostatectomy for prostate cancer[J]. Eur Urol, 2012,61(3):455-466.
[12] Schwen ZR, Tosoian JJ, Sokoll LJ , et al. Prostate Health Index (PHI) Predicts High-stage Pathology in African American Men[J]. Urology, 2016,90:136-140.
[13] Dolejsova O, Kucera R, Fuchsova R , et al. The ability of Prostate Health Index (PHI) to predict gleason score in patients with prostate cancer and discriminate patients between gleason score 6 and gleason score higher than 6: a study on 320 patients after radical prostatectomy[J]. Technol Cancer Res Treat, 2018,17:1-6.
[14] Chiu PK, Lai FM, Teoh JY , et al. Prostate health index and %p2PSA predict aggressive prostate cancer pathology in Chinese[J]. Ann Surg Onclo, 2016,23(8):2707-2714.
[15] 王友林, 朱磊一, 姜波 , 等. 超声引导下经直肠前列腺穿刺与前列腺癌根治术后病理组织Gleason评分差异性的研究[J]. 临床泌尿外科杂志, 2015,30(7):628-630.
[1] 白杲琛,宋毅,金杰,虞巍,何志嵩. 多西他赛联合卡铂治疗转移性去势抵抗性前列腺癌的临床疗效[J]. 北京大学学报(医学版), 2021, 53(4): 686-691.
[2] 徐涛,韩敬丽,姚伟娟. 雄激素剥夺治疗相关心血管疾病的机制与临床对策[J]. 北京大学学报(医学版), 2020, 52(4): 607-609.
[3] 李文卿,任思楣,龙星博,田雨青. 棕榈酰化蛋白质组学分析揭示前列腺癌细胞中雄激素促进代谢相关蛋白棕榈酰化修饰[J]. 北京大学学报(医学版), 2020, 52(2): 227-233.
[4] 张宽根,周雨禾,邵雅昆,梅放,由江峰,刘北英,裴斐. 肿瘤转移抑制基因LASS2/TMSG1 S248A突变体通过增加ATP6V0C表达促进前列腺癌的侵袭[J]. 北京大学学报(医学版), 2019, 51(2): 210-220.
[5] 唐旭,赵卫红,宋琴琴,殷华奇,杜依青,盛正祚,王强,张晓威,李清,刘士军,徐涛. SOX10对前列腺癌细胞增殖及侵袭的影响[J]. 北京大学学报(医学版), 2018, 50(4): 602-606.
[6] 邹鹏程,杨一峰,徐晓艳,刘北英,梅放,由江峰,刘启忱,裴斐 . 沉默液泡型ATP酶c亚基ATP6V0C抑制人前列腺癌细胞侵袭的分子机制[J]. 北京大学学报(医学版), 2017, 49(6): 937-947.
[7] 纪光杰,黄聪,宋刚,李学松,宋毅,周利群. 去势抵抗性前列腺癌进展时间的预测因素分析[J]. 北京大学学报(医学版), 2017, 49(4): 657-662.
[8] 杨恺惟, 虞巍, 宋毅, 黄立华, 韩文科, 何志嵩, 金杰, 周利群. 影响多西他赛联合泼尼松治疗转移性去势抵抗性前列腺癌疗效的因素分析[J]. 北京大学学报(医学版), 2015, 47(4): 592-596.
[9] 刘汀, 王霄英, 王义. 用Cox模型对前列腺癌相关临床检查的多因素生存分析[J]. 北京大学学报(医学版), 2009, 41(2): 184-187.
[10] 尚永丰. 核受体对基因转录的调控[J]. 北京大学学报(医学版), 2002, 34(5): 440-450.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 田增民, 陈涛, Nanbert ZHONG, 李志超, 尹丰, 刘爽. 神经干细胞移植治疗遗传性小脑萎缩的临床研究(英文稿)[J]. 北京大学学报(医学版), 2009, 41(4): 456 -458 .
[2] 成刚, 钱振华, 胡军. 艾滋病项目自愿咨询检测的技术效率分析[J]. 北京大学学报(医学版), 2009, 41(2): 135 -140 .
[3] 卢恬, 朱晓辉, 柳世庆, 郑杰, 邱晓彦. 白细胞介素2促进宫颈癌细胞系HeLaS3免疫球蛋白G的表达[J]. 北京大学学报(医学版), 2009, 41(2): 158 -161 .
[4] 袁惠燕, 张苑, 范田园. 离子交换型栓塞微球及其载平阳霉素的制备与性质研究[J]. 北京大学学报(医学版), 2009, 41(2): 217 -220 .
[5] 徐莉, 孟焕新, 张立, 陈智滨, 冯向辉, 释栋. 侵袭性牙周炎患者血清中抗牙龈卟啉单胞菌的IgG抗体水平的研究[J]. 北京大学学报(医学版), 2009, 41(1): 52 -55 .
[6] 董稳, 刘瑞昌, 刘克英, 关明, 杨旭东. 氯诺昔康和舒芬太尼用于颌面外科术后自控静脉镇痛的比较[J]. 北京大学学报(医学版), 2009, 41(1): 109 -111 .
[7] 祁琨, 邓芙蓉, 郭新彪. 纳米二氧化钛颗粒对人肺成纤维细胞缝隙连接通讯的影响[J]. 北京大学学报(医学版), 2009, 41(3): 297 -301 .
[8] Jian-wei GU, Emily YOUNG, Zhi-jun PAN, Kevan B. TUCKER, Megan SHPARAGO, Min HUANG, Amelia Purser BAILEY. SD大鼠长期高盐饮食可导致其高血压并改变肾细胞因子基因表达谱[J]. 北京大学学报(医学版), 2009, 41(5): 505 -515 .
[9] 李宏亮*, 安卫红*, 赵扬玉, 朱曦. 妊娠合并高脂血症性胰腺炎行血液净化治疗1例[J]. 北京大学学报(医学版), 2009, 41(5): 599 -601 .
[10] 李伟军, 邢晓芳, 曲立科, 孟麟, 寿成超. PRL-3基因C104S位点突变体和CAAX缺失体的构建及表达[J]. 北京大学学报(医学版), 2009, 41(5): 516 -520 .