PCA3 (Prostate cancer associated 3)

Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology.

Methodology: A descriptive research centered on genetic biomarkers associated with the diagnosis of prostate cancer was conducted.The selection of articles comprised the period from 2019 to 2024, using as an inclusion criterion those available in the PubMed database, from the descriptor: Prostate cancer biomarkers being 519 articles, being selected only 15 Results Over the years, several studies have identified genetic tests such as BRCA1 and BRCA2, capable of identifying patients at high risk of developing prostate cancer.These findings culminated in the identification of new genetic biomarkers, categorized as blood and urinary.Urinary markers, such as Select MDX, MIPS, Exodx Prostate and PCA3-PCGm1, improve early diagnosis, reducing the need for invasive prostate biopsies, dispensing rectal touch.Already the blood markers, exemplified by the 4kscore test, associate themselves with algorithms, expanding their potential when employed in conjunction with magnetic resonance imaging and the prostate health index. Conclusion The introduction of genetic biomarkers in the context of prostate cancer represents a significant advance, providing subsidies to improve the detection, diagnosis and risk assessment associated with this neoplasia.Its application in clinical practice emerges as a facilitating tool in decision making regarding the indication of biopsies and rebiopsies, contributing to the reduction of invasive procedures and giving greater accuracy to the diagnostic process.

Risk factors for prostate cancer bone metastases include elevated PSA and PCA3 levels as well as elevated ADCmean and big ADCdiffer. The combination of PSA, PCA3, and MRI ADC values demonstrated a strong predictive value for bone metastasis in prostate cancer patients.

Finally, pharmacological inhibition of REC-activity drastically inhibited PCa-cell aggressiveness. Altogether, the REC is drastically dysregulated in PCa, wherein this novel molecular event/mechanism, especially PABPN1 alteration, may be potentially exploited as a novel prognostic and therapeutic tool for PCa.

We also briefly discuss a few promising biofluid marker candidates (DNA methylation, micro-RNAs) which are not in clinical application. As no single assay is perfect, we envision that a combination of biomarkers, together with imaging, will become the preferred practice.

This work illustrates the importance of correcting for cell types of the TME when performing EWASs and DEAs on PCa samples, and establishes a more confounding-adverse methodology. We identified a more tumor-cell-specific set of altered genes and epigenetic marks that can be further investigated as potential biomarkers of disease or potential therapeutic targets.

Regarding the detection of csPCa, 4K had the highest diagnostic performance among the commercial liquid biomarkers. Based on the optimal thresholds calculated by the present meta-analysis, 4K had the highest sensitivity and PHI had the highest specificity for detecting csPCa. Nevertheless, clinical decision-making requires combination strategies between liquid and imaging biomarkers.

"Genetic alterations frequently identified in PCa, including BRCA1/BRCA2, ETS gene fusions, and AR changes, are also discussed, offering insights into risk assessment and precision treatment strategies. By evaluating the latest developments and applications of PCa biomarkers, this review contributes to an enhanced understanding of their role in disease management."

Overall, the study results indicated that total PSA and PCA3 levels have higher diagnostic accuracy in distinguishing patients with suspected prostate cancer from healthy individuals.

P1/2, N=24, Active, not recruiting, Orca Therapeutics B.V. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Nov 2023 --> Oct 2024

In the prospective active surveillance cohort (n = 182), C at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, C is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

Androgen deprivation and hormonal therapy are evolving as new and better options for managing hormone-sensitive and castration-resistant PC. This review aimed to highlight and discuss epidemiology, various risk factors, and developments in PC diagnosis and treatment regimens.

This study revealed seven potential pathways of Enhancer of Zeste Homolog 2 (EZH2)-related ceRNA mechanisms: lncRNA (SNHG3, 6) -Mir-101-3P-ezh2; lncRNA (SNHG12, RNF216P1)-let-7c-5p-EZH2. We also analyzed the immunity and drug sensitivity of EZH2. Our study proves that EZH2 still has great research prospects in HCC.

EV-H19 may negatively correlate with AR-signaling activity and could be a marker to diagnose ARAT-resistance among CRPC patients.

PCA3 served as a biomarker of CAS and regulates the function of VSMCs through sponging miR-124-3p/ITGB1 and indirectly influence the stability of plaque.

We show that the assay allows the detection of miR-141 in human serum, even in the presence of other miRNAs, with a LOD of 0.25 pM. The developed electrochemiluminescent assay has, therefore, the potential for efficient universal oligonucleotide target detection via the redesign of capture and detection probes.

Since testing for variations in genomic regions encoding non-coding RNAs offers a promising approach for cancer testing, identification and interpretation of single nucleotide polymorphisms associated with prostate cancer susceptibility is of great interest. Accordingly, here, for the first time, we review and discuss current available knowledge about genomic variation of long non-coding RNA molecules in prostate cancer.

P=N/A, N=306, Recruiting, Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori | Trial completion date: Jan 2022 --> Jan 2024 | Trial primary completion date: Jan 2022 --> Jan 2024

Tumors communicate with platelets by means of sEVs, which deliver cancer markers and activate platelets in a CD63-dependent manner leading to thrombosis. This emphasizes the diagnostic and prognostic value of platelet-associated cancer markers and identifies new pathways for intervention.

We also evaluated the related signaling pathways and the significance of these RNAs in prediction of survival of patients with prostate cancer. This study provides novel candidates for construction of specific treatment routes for prostate cancer.

For the purpose of using polyphenols in cancer therapy, it would be helpful to have more in-depth knowledge about lncRNA modulation via resveratrol. Here, we discuss the current knowledge and future promise of resveratrol as modulators of lncRNAs in different cancers.

Coverage of novel CaP biomarkers are relatively robust for Medicare plans but sparse for non-Medicare plans, with the majority of non-Medicare plans requiring prior authorization. Non-Medicare eligible men may face significant barriers to obtaining these tests.

PCA3 score detected in urine demonstrated moderate sensitivity and good specificity in differentiation between PCa and non-PCa and high sensitivity and specificity in differentiation between clinically significant PCa and non-PCa.

We also performed a Kruskal-Wallis test; however, there was no significant relationship between PSA (p=0.236), TMPRSS2:ERG (p=0.801), and PCA3 (p=0.091) with the Gleason score. There is a significant correlation between overexpression of PSA, TMPRSS2:ERG and PCA3 with the incidence of prostate cancer, and TMPRSS2:ERG and PCA3 can be used as biomarkers of prostate cancer.

P=N/A, N=20, Recruiting, Hospices Civils de Lyon | Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2023 --> Mar 2024

PSA is currently the most widely used biomarker as a screening method for prostate cancer. Additional studies of new biomarkers in patients need to be evaluated for better screening and thus clinical management.

LncRNAs can contribute to the pathogenesis of prostate cancer via modulation of androgen receptor (AR) signaling, ubiquitin-proteasome degradation process of AR or other important signaling pathways. The current review summarizes the role of lncRNAs in the evolution of prostate cancer with an especial focus on their importance in design of novel biomarker panels and therapeutic targets.

We report a highly accurate panel of 3 urine-based biomarkers that detect PCa consisting of EpCAM (protein) and TTC3 and H4C5 (RNA). To identify the advantage of using individual or combinatorial markers is an ongoing study in our laboratory.

P=N/A, N=243, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2022 --> Dec 2023

We report a highly accurate panel of 3 urine-based biomarkers that detect PCa consisting of EpCAM (protein) and TTC3 and H4C5 (RNA). To identify the advantage of using individual or combinatorial markers is an ongoing study in our laboratory.

P=N/A, N=120, Active, not recruiting, CHU de Quebec-Universite Laval | Trial primary completion date: Dec 2022 --> Dec 2023

The five housekeeping genes were not significantly differentially expressed between PCa and non-cancer samples. Expression signatures from Cell, EV and combined data did not show evidence for one fraction providing superior information over the other.

Another potential direction that has emerged to aid in the CaP diagnosis include multi-parametric magnetic resonance imaging (mpMRI) and bi-parametric magnetic resonance imaging (bpMRI), which in conjunction with clinically validated biomarkers may provide a better approach to predict clinically significant CaP at diagnosis. In this review, we discuss some of the adjunctive biomarker tests along with newer imaging modalities that are currently available to help clinicians decide which patients are at risk of having high-grade CaP on prostate biopsy with the emphasis on clinical utility of the tests across African American (AA) and Caucasian (CA) men.

We have discovered that METCAM, a cell adhesion molecule in the Ig-like superfamily, has great potential regarding its use as a biomarker for differentiating prostate cancer from BPH, predicting the malignant propensity of prostate cancer at the early premalignant stage, and differentiating indolent prostate cancers from aggressive cancers. Since METCAM has also been shown to be able to initiate the spread of prostate cancer cell lines to multiple organs, we suggest that it may be used as a therapeutic target for the clinical treatment of patients with malignant prostate cancer.

We found that screening men at high genetic risk for PCa must be based on mpMRI without pre-screening based on PSA>3ng/mL, to avoid missing too much ISUP>1 tumours and to significantly reduce the number of unnecessary biopsies. However, urinary markers or PSAD≥0.1ng/mL/cc when mpMRI was negative increased the detection of ISUP>1 cancers. We suggest that a baseline mpMRI be discussed for men at high genetic risk from 40 years-old.

EDN reports research fellowship support from the Brazilian National Council for Scientific and Technological Development (CNPq), Brazil, and the Associação Beneficente Alzira Denise Hertzog Silva (ABADHS), Brazil. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of New Mexico Comprehensive Cancer Center (CA118100) and the Rutgers Cancer Institute of New Jersey (CA072720).

Nonetheless, our findings corroborate tissue-based molecular data demonstrating ERG is less overexpressed in AA men’s tumors. These data underscore the importance of considering race in the development of PCa biomarkers.

This is the first time that the role of S100A4 and MRC2 has been described in PC aggressiveness. Moreover, the combination of S100A4, MRC2, and PCA3 has never been described as a non-invasive biomarker for PC screening and aggressiveness.

Both surface and genetic biomarkers should be validated for a more accurate prognosis in prostate cancer.

According to the ROC analysis, the expression levels of 19 hub genes showed a high diagnostic value. Taken together, we introduce a number of novel promising diagnostic biomarkers for prostate cancer.