Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (2): 234-239. doi: 10.19723/j.issn.1671-167X.2020.02.007

Previous Articles     Next Articles

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

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

CLC Number: 

  • R737.2

Table 1

Basic data for PCa patients with different Gleason score"

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

Table 2

Value of each index for predicting PCa patients (in total) with Gleason score≥7"

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

Figure 1

ROC curves for each index to predict PCa patients (in total) with Gleason score≥7 tPSA, total prostate-specific antigen; fPSA, free prostate-specific antigen; f/t, fPSA/tPSA; p2PSA, isoform [-2] proprostate-specific antigen; %p2PSA, p2PSA/(fPSA×1 000)×100; PHI, prostate health index."

Table 3

Value of each index for predicting PCa patients (identified by biopsy) with Gleason score≥7"

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

Figure 2

ROC curves for each index to predict PCa patients (identified by biopsy) with Gleason score≥7 tPSA, total prostate-specific antigen;fPSA, free prostate-specific antigen; f/t, fPSA/tPSA; p2PSA, isoform [-2] proprostate-specific antigen; %p2PSA, p2PSA/(fPSA×1 000)×100; PHI, prostate health index."

Table 4

Value of each index for predicting PCa patients (received radical prostatectomy) with Gleason score≥7"

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

Figure 3

ROC curves for each index to predict PCa patients (received radical prostatectomy) with Gleason score≥7 tPSA, total prostate-specific antigen; fPSA, free prostate-specific antigen; f/t, fPSA/tPSA; p2PSA, isoform [-2] proprostate- specific antigen; %p2PSA, p2PSA/(fPSA×1 000)×100; PHI, prostate health index."

[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] BAI Gao-chen,SONG Yi,JIN Jie,YU Wei,HE Zhi-song. Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer [J]. Journal of Peking University (Health Sciences), 2021, 53(4): 686-691.
[2] Wen-qing LI,Si-mei REN,Xing-bo LONG,Yu-qing TIAN. Palmitoylome profiling indicates that androgens promote the palmitoylation of metabolism-related proteins in prostate cancer-derived LNCaP cells [J]. Journal of Peking University (Health Sciences), 2020, 52(2): 227-233.
[3] Kuan-gen ZHANG,Yu-he ZHOU,Ya-kun SHAO,Fang MEI,Jiang-feng YOU,Bei-ying LIU,Fei PEI. Novel tumor metastasis suppressorgene LASS2/TMSG1 S248A mutant promotes invasion of prostate cancer cells through increasing ATP6V0C expression [J]. Journal of Peking University(Health Sciences), 2019, 51(2): 210-220.
[4] TANG Xu, ZHAO Wei-hong, SONG Qin-qin, YIN Hua-qi, DU Yi-qing, SHENG Zheng-zuo, WANG Qiang, ZHANG Xiao-wei, LI Qing, LIU Shi-jun, XU Tao. Influence of SOX10 on the proliferation and invasion of prostate cancer cells [J]. Journal of Peking University(Health Sciences), 2018, 50(4): 602-606.
[5] ZOU Peng-cheng, YANG Yi-feng, XU Xiao-yan LIU Bei-ying, MEI Fang, YOU Jiang-feng, LIU Qi-chen, PEI Fei . Silencing of vacuolar ATPase c subunit ATP6V0C inhibits invasion of prostate cancer cells [J]. Journal of Peking University(Health Sciences), 2017, 49(6): 937-947.
[6] JI Guang-jie, HUANG Cong, SONG Gang, LI Xue-song, SONG Yi, ZHOU Li-qun. Predictive factor analysis of time to progression of castration-resistant prostate cancer after androgen deprivation therapy [J]. Journal of Peking University(Health Sciences), 2017, 49(4): 657-662.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] . [J]. Journal of Peking University(Health Sciences), 2009, 41(4): 456 -458 .
[2] . [J]. Journal of Peking University(Health Sciences), 2009, 41(2): 135 -140 .
[3] . [J]. Journal of Peking University(Health Sciences), 2009, 41(2): 158 -161 .
[4] . [J]. Journal of Peking University(Health Sciences), 2009, 41(2): 217 -220 .
[5] . [J]. Journal of Peking University(Health Sciences), 2009, 41(1): 52 -55 .
[6] . [J]. Journal of Peking University(Health Sciences), 2009, 41(1): 109 -111 .
[7] . [J]. Journal of Peking University(Health Sciences), 2009, 41(3): 297 -301 .
[8] . [J]. Journal of Peking University(Health Sciences), 2009, 41(5): 505 -515 .
[9] . [J]. Journal of Peking University(Health Sciences), 2009, 41(5): 599 -601 .
[10] . [J]. Journal of Peking University(Health Sciences), 2009, 41(5): 516 -520 .