PCA3 as a second-line biomarker in a prospective controlled randomized opportunistic prostate cancer screening programme

Rubio‐Briones, J.; Casanova, J.; Martínez, Fernando; Domínguez-Escrig, José; Fernández-Serra, Antonio; Dumont, R.; Ramírez‐Backhaus, M.; Gómez-Ferrer, Á.; Collado, A.; Rubio, Luis; Molina, A.; Vanaclocha, Mercedes; Sala, Danila Cristina Paquier; Löpez‐Guerrero, José Antonio

doi:10.1016/j.acuroe.2017.04.003

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…Another concern is thus far only a small portion of lncRNAs and circRNAs has been studied. Unlike miRNA that is broadly expressed in most of cells, some lncRNAs, such as PCA3, are specifically expressed in cancer cells [121]. This may make them good targets for novel therapy.…”

Section: Perspective: Ncrnas As Potential Targets For Immunotherapiesmentioning

confidence: 99%

Noncoding RNAs in cancer immunity: functions, regulatory mechanisms, and clinical application

Zhang

2020

Mol Cancer

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It is well acknowledged that immune system is deeply involved in cancer initiation and progression, and can exert both pro-tumorigenic and anti-tumorigenic effects, depending on specific microenvironment. With the better understanding of cancer-associated immune cells, especially T cells, immunotherapy was developed and applied in multiple cancers and exhibits remarkable efficacy. However, currently only a subset of patients have responses to immunotherapy, suggesting that a boarder view of cancer immunity is required. Non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are identified as critical regulators in both cancer cells and immune cells, thus show great potential to serve as new therapeutic targets to improve the response of immunotherapy. In this review, we summarize the functions and regulatory mechanisms of ncRNAs in cancer immunity, and highlight the potential of ncRNAs as novel targets for immunotherapy. Development of cancer immunology Cancer immunology was discovered by William Coley who speculated that a strep infection had reversed cancer growth in 1891 [10]. Over time, many studies have confirmed that homograft rejection could reject transplanted tumors [11-13]. Based on this viewpoint, in 1970 Macfarlane Burnet developed and systematically

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Section: Perspective: Ncrnas As Potential Targets For Immunotherapiesmentioning

confidence: 99%

Noncoding RNAs in cancer immunity: functions, regulatory mechanisms, and clinical application

Zhang

2020

Mol Cancer

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“…After screening titles and abstracts of relevant articles, 418 articles were excluded because these were not related to the inclusion criteria. Finally, 65 case-control studies published between 2003 and 2018 were included in the meta-analysis (11)(12)(13)(14)(15)(16)(17)(18). All of these studies were retrospective in design.…”

Section: Studies Characteristicsmentioning

confidence: 99%

“…As a noninvasive diagnostic urine test, prostate cancer gene 3 (PCA3) is more accurate than PSA and can reduce the likelihood of false-positive results (11). Up to present, numerous individual studies have been performed to explore the diagnostic value of urine PCA3 in the management of PCa (12)(13)(14)(15)(16)(17)(18). However, these studies on the diagnostic performance of PCA3 have reported unclear or even conflicting results.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis

Qin

Yao

et al. 2020

Int. braz j urol.

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Background: The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. Materials and Methods: A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR−), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. Results: With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR−, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. Conclusions: The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.

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“…We previously demonstrated how to improve an opportunistic screening for PCa detection using PCA3 as a single biomarker after PSA and DRE in patients with PSA ≥ 3 ng/mL, 12 but did not achieve sufficient accuracy for detection of grade group 2 (GG2) PCa. We then tested PCA3 within a previously published nomogram 13 and validated its usefulness when added to standard risk factors to improve significantly the discrimination ability of a predictive model of high‐grade PCa with some lower statistical power compared with the generation cohort 14 …”

Section: Introductionmentioning

confidence: 99%

Validation of a 2‐gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population

et al. 2020

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Background: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. Methods:We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis.Results: In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk.Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies Jose Rubio-Briones and Ángel Borque-Fernando contributed equally to this study. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section. How to cite this article: Rubio-Briones J, Borque-Fernando A, Esteban LM, et al. Validation of a 2-gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population. The Prostate. 2020;80:500-507.

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PCA3 as a second-line biomarker in a prospective controlled randomized opportunistic prostate cancer screening programme

Cited by 6 publications

References 38 publications

Noncoding RNAs in cancer immunity: functions, regulatory mechanisms, and clinical application

Noncoding RNAs in cancer immunity: functions, regulatory mechanisms, and clinical application

Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis

Validation of a 2‐gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population

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