Startseite Prostate cancer antigen 3 (PCA3) RNA detection in blood and tissue samples for prostate cancer diagnosis
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Prostate cancer antigen 3 (PCA3) RNA detection in blood and tissue samples for prostate cancer diagnosis

  • Adriana F. Neves EMAIL logo , Jaqueline D. Dores Dias-Oliveira , Thaise G. Araújo , Karina Marangoni und Luiz R. Goulart
Veröffentlicht/Copyright: 8. Dezember 2012
Veröffentlichen auch Sie bei De Gruyter Brill

Abstract

Background: The non-coding prostate cancer antigen 3 (PCA3) RNA is currently the most specific biomarker for prostate cancer (PCa) diagnosis. Although its clinical value has been validated in a urine assay after intensive prostatic massage, few studies have been conducted to establish its diagnostic value in the peripheral blood (PBL). The aim of the present study was to examine the PCA3 expression in blood as a diagnostic tool, and to provide an additional strategy to improve PCa diagnosis.

Methods: PCA3 transcripts were detected by RT-PCR in PBL and prostatic tissues from patients. PBL sampling also included a group of young healthy volunteers. The relationship between the PCA3 RNA detection and clinical characteristics was analyzed.

Results: PCA3 detection in blood presented 94% specificity and 32% sensitivity, and its combined detection in tissues significantly improved diagnostic parameters. However, PCA3 RNA detection in blood was also associated with PSA levels ≥10 ng/mL, and their combination provided a sensitivity of 60% and specificity of 93%.

Conclusions: Detection of the PCA3 RNA in patients’ blood is an efficient tool for PCa diagnosis because it allows a routine collection procedure, which is also supported by the ongoing screening marker, prostate-specific antigen (PSA). We propose its combined use with PSA levels ≥10 ng/mL, which improves accuracy, and prevents overdiagnosis and overtreatment.


Corresponding author: Adriana F. Neves, PhD, Molecular Genetics and Biotechnology Laboratory, Department of Biological Sciences, Federal University of Goias, 75.704–020, Catalao, GO, Brazil, Phone: + 55 64 34415348, Fax: + 55 64 34415300

The authors would like to thank the Urology Division of the University Hospital of Uberlandia for providing the biological samples, especially to the urologist Danielo Garcia de Freitas, and the pathologist Tania M. Alcântara. We would also like to thank BioGenetics Molecular Technologies Ltda, CAPES, CNPq, FAPEMIG, and FAPEG for their financial support.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Financial support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics CA cancer. J Clin 2011;61:69–90.10.3322/caac.20107Suche in Google Scholar

2. Buhmeida A, Pyrhönen S, Laato M, CollanY. Prognostic factors in prostate cancer. Diagn Pathol 2006;1:4.10.1186/1746-1596-1-4Suche in Google Scholar PubMed

3. Bickers B, Aukim-Hastie C. New molecular biomarkers for the prognosis and management of prostate cancer – the post PSA era. Anticancer Res 2009;29:3289–98.Suche in Google Scholar PubMed

4. Strittmatter F, Stieber P, Nagel D, Füllhase C, Walther S, Stief CG, et al. Detection of prostate cancer with complexed PSA and complexed/total PSA ratio – is there any advantage? Eur J Med Res 2011;16:445–50.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000296748400004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1186/2047-783X-16-10-445Suche in Google Scholar PubMed

5. Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, Fu R, et al. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2011;155:762–71.10.7326/0003-4819-155-11-201112060-00375Suche in Google Scholar PubMed

6. Salami SS, Schmidt F, Laxman B, Regan MM, Rickman DS, Scherr D, et al. Combining urinary detection of TMPRSS2: ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer. Urol Oncol 2011. Epub ahead of print 19 May 2011. DOI:10.1016/j.urolonc.2011.04.001.10.1016/j.urolonc.2011.04.001Suche in Google Scholar

7. Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, et al. DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 1999;59:5975–9.Suche in Google Scholar PubMed

8. Schalken JA, Hessels D, Verhaegh G. New targets for therapy in prostate cancer: differential display code 3 (DD3(PCA3)), a highly prostate cancer-specific gene. Urology 2003;62:34–43.10.1016/S0090-4295(03)00759-3Suche in Google Scholar

9. Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA, Aalders TW, et al. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 2002;62: 2695–8.Suche in Google Scholar PubMed

10. Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, et al. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol 2003;44:8–15.10.1016/S0302-2838(03)00201-XSuche in Google Scholar PubMed

11. Hessels D, van Gils MP, van Hooij O, Sander A, Jannink SA, Witjes JA, et al. Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer. Prostate 2010;70:10–6.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000273471800002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1002/pros.21032Suche in Google Scholar PubMed

12. Fontenete S, Silva J, Teixeira AL, Ribeiro R, Bastos E, Pina F, et al. Controversies in using urine samples for prostate cancer detection: PSA and PCA3 expression analysis. Int Braz J Urol 2011;37:719–26.10.1590/S1677-55382011000600006Suche in Google Scholar PubMed

13. Oliveira JD, Goulart LR, Waldesse PO, Meola J, Neves AF. DD3 gene expression in peripheral blood of patients with prostate cancer and with benign prostate hyperplasia as a molecular diagnostic. Eur Urol 2003;2(Suppl):S102.10.1016/S1569-9056(03)90463-5Suche in Google Scholar

14. Väänänen RM, Rissanen M, Kauko O, Junnila S, Väisänen V, Nurmi J, et al. Quantitative real-time RT-PCR assay for PCA3. Clin Biochem 2008;41:103–8.10.1016/j.clinbiochem.2007.10.009Suche in Google Scholar PubMed

15. Jost M, Day JR, Slaughter R, Koreckij TD, Gonzales D, Kinnunen M, et al. Molecular assays for the detection of prostate tumor derived nucleic acids in peripheral blood. Mol Cancer 2010;9:174.10.1186/1476-4598-9-174Suche in Google Scholar PubMed

16. Llanes L, Ferruelo A, Páez A, Gómez JM, Moreno A, Berenguer A. The clinical utility of the prostate specific membrane antigen reverse-transcription/polymerase chain reaction to detect circulating prostate cells: an analysis in healthy men and women. Br J Urol Int 2002;89:882–5.10.1046/j.1464-410X.2002.02774.xSuche in Google Scholar

17. Martínez-Piñeiro L, Rios E, Martínez-Gomariz M, Pastor T, de Cabo M, Picazo ML, et al. Molecular staging of prostatic cancer with RT-PCR assay for prostate-specific antigen in peripheral blood and lymph nodes: comparison with standard histological staging and immunohistochemical assessment of occult regional lymph node metastases. Eur Urol 2003;43:342–50.10.1016/S0302-2838(03)00055-1Suche in Google Scholar

18. Kurek R, Nunez G, Tselis N, Konrad L, Martin T, Roeddiger S, et al. Prognostic value of combined “triple”-reverse transcription-PCR analysis for prostate-specific antigen, human kallikrein 2, and prostate-specific membrane antigen mRNA in peripheral blood and lymph nodes of prostate cancer patients. Clin Cancer Res 2004;10:5808–14.10.1158/1078-0432.CCR-1004-03Suche in Google Scholar

19. Mitsiades CS, Lembessis P, Sourla A, Milathianakis C, Tsintavis A, Koutsilieris M. Molecular staging by RT-PCR analysis for PSA and PSMA in peripheral blood and bone marrow samples is an independent predictor of time to biochemical failure following radical prostatectomy for clinically localized prostate cancer. Clin Exp Metastasis 2004;21:495–505.10.1007/s10585-004-3217-0Suche in Google Scholar

20. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol chloroform extraction. Anal Biochem 1987;62:156–9.10.1016/0003-2697(87)90021-2Suche in Google Scholar

21. Tao Z, Shen M, Zheng Y, Mao X, Chen Z, Yin Y, et al. PCA3 gene expression in prostate cancer tissue in a Chinese population: quantification by real-time FQ-RT-PCR based on exon 3 of PCA3. Exp Mol Pathol 2010;89:58–62.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000280019700008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1016/j.yexmp.2010.01.008Suche in Google Scholar PubMed

22. Neves AF, Araújo TG, Biase WK, Meola J, Alcântara TM, Freitas DG, et al. Combined analysis of multiple mRNA markers by RT-PCR assay for prostate cancer diagnosis. Clin Biochem 2008;41:1191–8.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000260486900012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1016/j.clinbiochem.2008.06.013Suche in Google Scholar PubMed

23. George J, Gondi CS, Dinh DH, Gujrati M, Rao JS. Restoration of tissue factor pathway inhibitor-2 in a human glioblastoma cell line triggers caspase-mediated pathway and apoptosis. Clin Cancer Res 2007;13:3507–17.10.1158/1078-0432.CCR-06-3023Suche in Google Scholar PubMed PubMed Central

24. Ruijter E, van de Kaa C, Miller G, Ruiter D, Debruyne F, Schalken J. Molecular genetics and epidemiology of prostate carcinoma. Endocr Rev 1999;20:22–45.10.1210/er.20.1.22Suche in Google Scholar

Received: 2012-06-19
Accepted: 2012-11-08
Published Online: 2012-12-08
Published in Print: 2013-04-01

©2013 by Walter de Gruyter Berlin Boston

Artikel in diesem Heft

  1. Letters to the Editor
  2. Missing agreement between the two IMMULITE® PSA assays
  3. “Cerebrovascular stressing”: dipyridamole-induced S100B elevation predicts ischemic cerebrovascular events
  4. Discrepancy in lamellar body counts (LBCs) between the Sysmex XE-2100 and Sysmex XT-2000i instruments
  5. Interphase fluorescent in situ hybridization detection of the 7q11.23 chromosomal inversion in a clinical laboratory: automated versus manual scoring
  6. Adrenocorticotropic hormone stability in preanalytical phase depends on temperature and proteolytic enzyme inhibitor
  7. The impact on costs and efficiency of reducing the number of collected tubes
  8. Improved software on the Sysmex XE-5000 BF mode for counting leukocytes in cerebrospinal fluid
  9. First trimester placental growth factor and soluble fms-like tyrosine kinase 1 are significantly related to PAPP-A levels
  10. Preliminary evaluation of complete blood cell count on Mindray BC-6800
  11. Rational use of laboratory tests: albuminuria
  12. Masthead
  13. Masthead
  14. Editorials
  15. Fifty years of CCLM – invitation to join us for a reception in Milan
  16. Personalized (laboratory) medicine: a bridge to the future
  17. PSA, PCA3 and the phi losophy of prostate cancer management
  18. Reviews
  19. Gender medicine: a task for the third millennium
  20. Evaluation of [−2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis
  21. Harmonization in laboratory medicine: the complete picture
  22. Opinion Papers
  23. Glycemic control in the clinical management of diabetic patients
  24. Time for a conceptual shift in assessment of internal quality control for whole blood or cell-based testing systems? An evaluation using platelet function and the PFA-100 as a case example
  25. Guidelines and Recommendations
  26. A position paper of the EFLM Committee on Education and Training and Working Group on Distance Education Programmes/E-Learning: developing an e-learning platform for the education of stakeholders in laboratory medicine
  27. General Clinical Chemistry and Laboratory Medicine
  28. A novel weighted cumulative delta-check method for highly sensitive detection of specimen mix-up in the clinical laboratory
  29. Identification and quantification of hemoglobins in whole blood: the analytical and organizational aspects of Capillarys 2 Flex Piercing compared with agarose electrophoresis and HPLC methods
  30. Determination of the fatty acid profile of neutral lipids, free fatty acids and phospholipids in human plasma
  31. Urinary iodine concentrations of pregnant women in Ukraine
  32. Delay in the measurement of eosin-5′-maleimide (EMA) binding does not affect the test result for the diagnosis of hereditary spherocytosis
  33. Faecal calprotectin: comparative study of the Quantum Blue rapid test and an established ELISA method
  34. Target analyte quantification by isotope dilution LC-MS/MS directly referring to internal standard concentrations – validation for serum cortisol measurement
  35. Reference Values and Biological Variations
  36. Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium
  37. Biological variation and reference change values of common clinical chemistry and haematologic laboratory analytes in the elderly population
  38. Indirect determination of pediatric blood count reference intervals
  39. Cancer Diagnostics
  40. Suitability of quality control materials for prostate-specific antigen (PSA) measurement: inter-method variability of common tumor marker control materials
  41. Prostate cancer antigen 3 (PCA3) RNA detection in blood and tissue samples for prostate cancer diagnosis
  42. Serum levels of cancer biomarkers in diabetic and non-diabetic proteinuric patients: a preliminary study
  43. Infectious Diseases
  44. Polymorphic mononuclear neutrophils CD64 index for diagnosis of sepsis in postoperative surgical patients and critically ill patients
  45. Plasma long pentraxin 3 (PTX3) concentration is a novel marker of disease activity in patients with community-acquired pneumonia
Heruntergeladen am 15.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/cclm-2012-0392/html
Button zum nach oben scrollen