Validation of proposed prostate cancer biomarkers with gene expression data: a long road to travel

# The Author(s) 2014. This article is published with open access at Springerlink.com Abstract Biomarkers are important for early detection of can-cer, prognosis, response prediction, and detection of residual or relapsing disease. Special attention has been given to diagnostic markers for prostate cancer since it is thought that early detection and surgery might reduce prostate cancer-specific mortality. The use of prostate-specific antigen, PSA (KLK3), has been debated on the base of cohort studies that show that its use in preventive screenings only marginally influences mortality from prostate cancer. Many groups have identified alternative or additional markers, among which PCA3, in order to detect early prostate cancer through screening, to distinguish potentially lethal from indolent prostate cancers, and to guide the treatment decision. The large number of markers proposed has led us to the present study in which we analyze these indicators for their diagnosti

Urinary biomarkers for prostate cancer: a review

Contains fulltext : 117921.pdf (publisher's version ) (Open Access)Although the routine use of serum prostate-specific antigen (PSA) testing has undoubtedly increased prostate cancer (PCa) detection, one of its main drawbacks is its lack of specificity. As a consequence, many men undergo unnecessary biopsies or treatments for indolent tumours. PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour. Since PCa is a heterogeneous disease, a panel of tumour markers is fundamental for a more precise diagnosis. Several biomarkers are promising due to their specificity for the disease in tissue. However, tissue is unsuitable as a possible screening tool. Since urine can be easily obtained in a non-invasive manner, it is a promising substrate for biomarker testing. This article reviews the biomarkers for the non-invasive testing of PCa in urine

The use of PCA3 in the diagnosis of prostate cancer.

Contains fulltext : 81148schalken.pdf (publisher's version ) (Closed access)Although the routine use of serum PSA testing has undoubtedly increased prostate cancer detection, one of its main drawbacks has been its lack of specificity, which results in a high negative biopsy rate. Consequently, a large population of men with chronically elevated serum PSA and one or more negative biopsies has emerged. More accurate tests are needed that can help identify which patients are at high risk of developing prostate cancer, and for whom repeat prostate biopsies are mandatory. To improve the specificity of prostate cancer diagnosis, prostate-cancer-specific markers, such as prostate cancer gene 3 (PCA3), are needed. The strong association between PCA3 mRNA overexpression and malignant transformation of prostate epithelium indicates its potential as a diagnostic biomarker. Quantification of PCA3 mRNA levels in urine was found to help predict the outcome of prostate biopsies. The intensive and time-consuming reverse-transcriptase polymerase chain reaction PCA3 urine test has been translated successfully into the fast and easy transcription-mediated amplification (TMA)-based PCA3 test. This test is the first RNA-based molecular diagnostic assay in body fluids for prostate cancer that is available to urologists. This Review describes the translation of the molecular marker PCA3 from the research laboratory to clinical practice

Controversies in using urine samples for prostate cancer detection: PSA and PCA3 expression analysis

PURPOSE: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. Although PSA utilization as a serum marker has improved prostate cancer detection it still presents some limitations, mainly regarding its specificity. The expression of this marker, along with the detection of PCA3 mRNA in urine samples, has been suggested as a new approach for PCa detection. The goal of this work was to evaluate the efficacy of the urinary detection of PCA3 mRNA and PSA mRNA without performing the somewhat embarrassing prostate massage. It was also intended to optimize and implement a methodological protocol for this kind of sampling. MATERIALS AND METHODS: Urine samples from 57 patients with suspected prostate disease were collected, without undergoing prostate massage. Increased serum PSA levels were confirmed by medical records review. RNA was extracted by different methods and a preamplification step was included in order to improve gene detection by Real-Time PCR. RESULTS: An increase in RNA concentration with the use of TriPure Isolation Reagent. Despite this optimization, only 15.8% of the cases showed expression of PSA mRNA and only 3.8% of prostate cancer patients presented detectable levels of PCA3 mRNA. The use of a preamplification step revealed no improvement in the results obtained. CONCLUSION: This work confirms that prostate massage is important before urine collection for gene expression analysis. Since PSA and PCA3 are prostate specific, it is necessary to promote the passage of cells from prostate to urinary tract, in order to detect these genetic markers in urine samples