Predict prostate cancer aggressiveness

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Aggressive cancer of the prostate - Prostate tumorale focusin comentarii

The focus has switched from one single marker PSA to panels of biomarkers including proteins involved in predict prostate cancer aggressiveness function and heat shock proteins. Novel genetic markers such as Transmembrane protease serine 2 TMPRSS2 -ERG fusion gene mRNA or prostate cancer gene 3 PCA3 had already entered the clinical practice, raising the question whether subsequent protein changes impact the evolution of the disease and the response to treatment.

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A new trend in prostate cancer research is proteomic analysis of prostasomes prostate-specific exosomesfor the discovery of new biomarkers. This paper provides an update of novel clinical tests used in research and clinical diagnostic, as well as of potential tissue or fluid biomarkers provided by extensive proteomic research data. Efforts are made continuously by researchers to investigate new potential biomarkers for a better risk stratification and personalized treatment strategy, given its variability in clinical behavior, treatment decisions and therapeutic responses [3].

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An important advancement in proteomics is the quantification of biomarkers, provided by new and powerful platforms, from both fluids urine, blood, seminal fluid and tissue [4]. This paper provides an overview of current most promising biomarkers identified with the new -omics technologies to help physicians in clinical decision making for PCa diagnosis, prognosis and prediction of therapeutic effect.

How do I know whether I have aggressive prostate cancer?

Prostate cancer PCa is the leading type of most common diagnosed urological cancer in men, and its prevalence is continuously increasing. Furthermore, PCa is currently the second leading cause of cancer-specific death in many countries [1].

It is usually diagnosed on the basis of digital rectal prostatita în sângele bărbaților DREprostate-specific antigen PSA serum levels and multicore schemes of prostate biopsy. Notably, PCa is a very heterogeneous disease characterized by different clinical behavior, from indolent to aggressive tumors with lethal progression.

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Therefore, early diagnostics and identification of PCa www. This test is offered by Mlabs, University of Michigan and was validated by numerous studies [13]. This non-invasive urinary test measures a panel of four metabolites alanine, glutamate, glycine, sarcosine by chromatography and mass spectrometry after a vigorous DRE. The Prostarix test showed increased sensitivity and specificity over serum PSA and its diagnostic accuracy was further improved by addition of clinical findings into a logistic regression model AUC 0.

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ConfirmMDx MDx Health, Irvine, CA is an epigenetic test that uses normal or benign prostate cores specimens for the prediction of a positive subsequent prostate biopsy to help patients to make adequate informed consent about the management of PCa at the initial diagnosis [16]. Its clinical utility to reduce the need for rebiopsy and detect latent disease was proven in several trial predict prostate cancer aggressiveness such as Matloc study or Document Study [13, 16].

An algorithm is generated by combining the blood test results with patient parameters age, DRE and previous biopsy results.

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For both scores, The discovery of PSA as a serum marker has revolutionized PCa diagnosis and nowadays is the only widely used PCa biomarker for diagnosis and prognosis of this disease. However, PSA is organ- but not cancer specific.

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Moreover, it is not able to differentiate between indolent and aggressive PCa. In addition, many men may harbor aggressive PCa disease despite having low initial value of serum PSA [5].

However, total PSA serum value together with Gleason score are the most significant variables to predict prostate cancer aggressiveness men at increased risk of PCa and are included in all nomograms for an accurate risk stratification of patients with PCa, both at the time of diagnosis and post-treatment [6]. Establishing the PCa aggressiveness and the optimal moment for therapeutic intervention are the primary end-points of the current clinical trials that are trying to identify new potential biomarkers for a better insight into PCa natural history [7].

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In the era of personalized medicine, a number of novel biomarkers become available to guide physicians in difficult clinical-decision making. A promising biomarker for PCa diagnosis is prostate cancer gene 3 PCA3 which is highly over-expressed by prostatic cancer cells.

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San Diego, CA, USA and is now commercially available for the use in patients with previous negative biopsy results for whom a repeat biopsy is considered by an urologist based on PSA level or DRE to predict positive biopsies malignancy. A score of less than 25 indicates a decrease probability of a positive repeat biopsy. This test was shown to be superior to total and free PSA for PCa diagnosis as demonstrated by numerous validation studies. For example, data from Deras et al.

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On the contrary, clinical utility and superiority of PCA3 was not demonstrated in patients undergoing first biopsy settings [9]. Also, it cannot distinguish between high grade PIN Prostatic Intraepithelial Neoplasia and PCa [10] and its utility as a prognostic test for PCa aggressiveness remain to be investigated.

However, recent data indicate that PCA3 has a promising role for monitoring in active surveillance since it can differentiate between high grade PIN and low-volume PCa [11].

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Oncotype DX® test Genomic Health, Inc, Redwood City, CA was developed as a biopsy-based genomic assay to predict adverse pathology and to distinguish between indolent and aggressive disease [19]. The test is a RT-PCR expression array of 12 genes implicated in PCa tumorigenesis angiogenesis, proliferation, cellular organization and stromal response and uses small 1 mm fixed paraffin-embedded tissue samples from needle biopsies.

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The Genomic Prostate Score [20]higher scores indicate more aggressive disease was externally validated as a significant predictor of aggressive disease and helps clinicians to identify high risk patients and start immediate adapted therapy. This assay measures the expression of 31 cell cycle progression CCP genes selected because of their demonstrated correlation with PCa proliferation, against 15 housekeeper genes from formalin-fixed paraffin-embedded tissue obtained by prostate biopsy or radical prostatectomy.

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The value of CCP test as a significant predictor for risk assessment beyond conventional clinic-pathological criteria on prostate biopsies and disease progression, recurrence, or prostate-cancer specific mortality on radical prostatectomy specimens was demonstrated in multiple cohorts [21].

Thus, it is an important tool for assessment of prognosis that helps clinicians to counsel their patients about how aggressive is disease prognosis and the need for close monitoring or adjuvant therapy [22].

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In this regard, clinical proteomics aims to identify and quantify new specific and sensitive biomarkers for PCa early detection, patient stratification and treatment efficacy. Many of these biomarkers were still need rigorous validation for being applied in clinical practice.

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In the last decades, a major progress was recorded on identification of thousands of proteins, as candidate biomarkers, in complex biological systems by newly proteomic approaches - mass spectrometry, 2D electrophoresis, multiplex assays and protein microarrays [24]. The utilization of proteomic signatures based on circulating biomarker panels represents an encouraging approach for efficient monitoring of disease progression, as well as therapy [25, 26].

Such studies were applied for serum samples [33, 34] or on urine samples [35].