Identification of Clinically Significant Prostate Cancer by Combined PCA3 and AMACR mRNA Detection in Urine Samples

• Main Authors: Kotova ES, Savochkina YA, Doludin YV, Vasilyev AO, Prilepskay EA, Potoldykova NV, Babalyan KA, Kanygina AV, Morozov AO, Govorov AV, Enikeev DV, Kostryukova ES, Ilina EN, Govorun VM, Pushkar DY, Sharova EI
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-09-01
• Series: Research and Reports in Urology
• Subjects: prostatic neoplasms; early diagnosis; neoplasm grading; alpha-methylacyl-coa racemase; rna.
• Online Access: https://www.dovepress.com/identification-of-clinically-significant-prostate-cancer-by-combined-p-peer-reviewed-article-RRU

Elena S Kotova,1 Yulia A Savochkina,2 Yuriy V Doludin,3 Alexander O Vasilyev,4 Elena A Prilepskay,4 Natalia V Potoldykova,3 Konstantin A Babalyan,1 Alexandra V Kanygina,1 Andrey O Morozov,3 Alexander V Govorov,4 Dmitry V Enikeev,3 Elena S Kostryukova,1 Elena N Ilina,1 Vadim M Govorun,1 Dmitry Y Pushkar,4 Elena I Sharova1 1Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia; 2Lytech Ltd, Moscow, Russia; 3Sechenov First Moscow State Medical University, Moscow, Russia; 4Department of Urology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, RussiaCorrespondence:Elena S KotovaDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Malaya Pirogovskaya 1a, Moscow 119992, RussiaTel [phone]Fax [phone]Email [e-mail]: Preclinical evaluation of PCA3 and AMACR transcript simultaneous detection in urine to diagnose clinical significant prostate cancer (prostate cancer with Gleason score ≥ 7) in a Russian cohort.Patients and Methods: We analyzed urine samples of patients with a total serum PSA ≥ 2 ng/mL: 31 men with prostate cancer scheduled for radical prostatectomy, 128 men scheduled for first diagnostic biopsy (prebiopsy cohort). PCA3, AMACR, PSA and GPI transcripts were detected by multiplex reverse transcription quantitative polymerase chain reaction, and the results were used for scores for calculation and statistical analysis.Results: There was no significant difference between clinically significant and nonsignificant prostate cancer PCA3 scores. However, there was a significant difference in the AMACR score (patients scheduled for radical prostatectomy p=0.0088, prebiopsy cohort p=0.029). We estimated AUCs, optimal cutoffs, sensitivities and specificities for PCa and csPCa detection in the prebiopsy cohort by tPSA, PCA3 score, PCPT Risk Calculator and classification models based on tPSA, PCA3 score and AMACR score. In the clinically significant prostate cancer ROC analysis, the PCA3 score AUC was 0.632 (95%CI: 0.511– 0.752), the AMACR score AUC was 0.711 (95%CI: 0.617– 0.806) and AUC of classification model based on the PCA3 score, the AMACR score and total PSA was 0.72 (95%CI: 0.58– 0.83). In addition, the correlation of the AMACR score with the ratio of total RNA and RNA of prostate cells in urine was shown (tau=0.347, p=6.542e– 09). Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use.Conclusion: The AMACR score is a good predictor of clinically significant prostate cancer. Significant amounts of nonprostate RNA in urine may be a limitation for the AMACR score use. Evaluation of the AMACR score and classification models based on it for clinically significant prostate cancer detection with larger samples and a follow-up analysis is promising.Keywords: prostatic neoplasms, early diagnosis, neoplasm grading, alpha-methylacyl-CoA racemase, RNA