What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective

Zapała, Piotr; Dybowski, Bartosz; Poletajew, Sławomir; Radziszewski, Piotr

doi:10.1159/000479982

Cited by 17 publications

(21 citation statements)

References 122 publications

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“…Few methylation‐based classifiers have been rigorously tested. Studies to date have small sample sizes and few have validated a DNA methylation‐based diagnostic classifier for prostate cancer. To date, only one epigenetic assay, ConfirmMDx, is commercially available, which measures methylation at APC , GSTP1 , and RASSF1 loci, and is intended for use on benign prostate biopsies to identify men who are likely to have cancer in a subsequent biopsy.…”

Section: Discussionmentioning

confidence: 99%

A three‐gene DNA methylation biomarker accurately classifies early stage prostate cancer

et al. 2019

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Background We identify and validate accurate diagnostic biomarkers for prostate cancer through a systematic evaluation of DNA methylation alterations. Materials and methods We assembled three early prostate cancer cohorts (total patients = 699) from which we collected and processed over 1300 prostatectomy tissue samples for DNA extraction. Using real‐time methylation‐specific PCR, we measured normalized methylation levels at 15 frequently methylated loci. After partitioning sample sets into independent training and validation cohorts, classifiers were developed using logistic regression, analyzed, and validated. Results In the training dataset, DNA methylation levels at 7 of 15 genomic loci (glutathione S‐transferase Pi 1 [GSTP1], CCDC181, hyaluronan, and proteoglycan link protein 3 [HAPLN3], GSTM2, growth arrest‐specific 6 [GAS6], RASSF1, and APC) showed large differences between cancer and benign samples. The best binary classifier was the GAS6/GSTP1/HAPLN3 logistic regression model, with an area under these curves of 0.97, which showed a sensitivity of 94%, and a specificity of 93% after external validation. Conclusion We created and validated a multigene model for the classification of benign and malignant prostate tissue. With false positive and negative rates below 7%, this three‐gene biomarker represents a promising basis for more accurate prostate cancer diagnosis.

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Section: Discussionmentioning

confidence: 99%

A three‐gene DNA methylation biomarker accurately classifies early stage prostate cancer

et al. 2019

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“…Several assays provide prognostic information for HGPC (GS ≥ 7) at Pbx, such as the serum assays (Prostate Health Index and 4Kscore), the DRE urine genetic tests (PCA3 and SelectMDx), the tPSA plus urinary PCA3 tests (MiPS), and first catch urine genetic test (EPI) . The reported AUC to evaluate the accuracy of predicting HGPC (GS ≥ 7) of these 6 assays ranged from 0.730 to 0.870, outperforming tPSA which has an AUC of 0.718 …”

Section: Introductionmentioning

confidence: 99%

Clinical significance of the LacdiNAc‐glycosylated prostate‐specific antigen assay for prostate cancer detection

et al. 2019

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To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc‐glycosylated prostate‐specific antigen (LDN‐PSA) and LDN‐PSA normalized by prostate volume (LDN‐PSAD). We retrospectively measured LDN‐PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop‐PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN‐PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN‐PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN‐PSA and LDN‐PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop‐PSA cohort, LDN‐PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc‐glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution (“The Study about Carbohydrate Structure Change in Urological Disease”; approval no. 2014‐195).

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“…However, such a classification for PCa based on protein expression does not exist yet. There are several biomarkers and biomarker assays on the market [6][7][8][9], but none of them have really arrived in the urologic clinic yet. Therefore, there is still a need to search for compelling biomarkers in PCa.…”

Section: Introductionmentioning

confidence: 99%

Expression of GP88 (Progranulin) Protein Is an Independent Prognostic Factor in Prostate Cancer Patients

Abdulrahman

Eckstein

Jung

et al. 2019

Cancers

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Prostate cancer, the second most common cancer, is still a major cause of morbidity and mortality among men worldwide. The expression of the survival and proliferation factor progranulin (GP88) has not yet been comprehensively studied in PCa tumors. The aim of this study was to characterize GP88 protein expression in PCa by immunohistochemistry and to correlate the findings to the clinico-pathological data and prognosis. Immunohistochemical staining for GP88 was performed by TMA with samples from 442 PCa patients using an immunoreactive score (IRS). Altogether, 233 cases (52.7%) with negative GP88 staining (IRS < 2) and 209 cases (47.3%) with positive GP88 staining (IRS ≥ 2) were analyzed. A significant positive correlation was found for the GP88 IRS with the PSA value at prostatectomy and the cytoplasmic cytokeratin 20 IRS, whereas it was negatively associated with follow-up times. The association of GP88 staining with prognosis was further studied by survival analyses (Kaplan–Meier, univariate and multivariate Cox’s regression analysis). Increased GP88 protein expression appeared as an independent prognostic factor for overall, disease-specific and relapse-free survival in all PCa patients. Interestingly, in the subgroup of younger PCa patients (≤65 years), GP88 positivity was associated with a 3.8-fold (p = 0.004), a 6.0-fold (p = 0.008) and a 3.7-fold (p = 0.003) increased risk for death, disease-specific death and occurrence of a relapse, respectively. In the PCa subgroup with negative CK20 staining, GP88 positivity was associated with a 1.8-fold (p = 0.018) and a 2.8-fold increased risk for death and disease-specific death (p = 0.028). Altogether, GP88 protein positivity appears to be an independent prognostic factor for PCa patients.

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What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective

Cited by 17 publications

References 122 publications

A three‐gene DNA methylation biomarker accurately classifies early stage prostate cancer

A three‐gene DNA methylation biomarker accurately classifies early stage prostate cancer

Clinical significance of the LacdiNAc‐glycosylated prostate‐specific antigen assay for prostate cancer detection

Expression of GP88 (Progranulin) Protein Is an Independent Prognostic Factor in Prostate Cancer Patients

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