BERKELEY, CA (UroToday.com) - The incidence of prostate cancer is rising steadily in most countries, and the commonly employed prostate-specific antigen (PSA) test once gave people hope for early diagnosis of prostate cancer. However, the low specificity of the PSA test has resulted in a large number of unnecessary biopsies and subsequent overtreatment. During the past decade, many new prostate cancer biomarkers have been found, and, among these, prostate cancer gene 3 (PCA3) is the most promising. PCA3, (also known as DD3) was mapped to chromosome 9q21-22, in antisense orientation within intron 6 of the prune homolog 2 gene. As a biomarker, is has fairly high specificity and sensitivity. Due to its outstanding performance in distinguishing prostate cancer from other prostate conditions, PCA3 could likely be applied for early diagnosis of prostate cancer, patient follow-up, prognostic prediction, and targeted therapy.
After years of research, we have obtained some knowledge about the sequence of PCA3 gene. We have also determined the relationship between PCA3 and the proliferation of prostate cancer cells and learned some information about how PCA3 affects tumor-related genes and proteins. PCA3 silencing decreases cell growth and survival and induces apoptotic cell death. Assays using the first voided urine following a digital rectal examination (DRE) have progressed significantly. Hessels et al. demonstrated for the first time the possibility of translating the PCa specificity of PCA3 at the tissue level into a specific test for diagnosis. They tested 108 urine samples and reported a sensitivity of 67%, specificity of 83%, positive predictive value of 53%, and negative predictive value of 90%. PCA3 mRNA and PSA mRNA can be detected in centrifuged urine sediment.
A PCA3 score is currently being used in some research studies. Unlike the PSA, the PCA3 is independent of prostate volume and whether a patient has had a prior biopsy or not, and it is unaffected by age. The PCA3 score is the ratio of PCA3 mRNA to PSA mRNA multiplied by 1000. PCA3 score can overcome the disadvantages of the low specificity of the traditional PSA test. Demonstrating the balance between specificity and sensitivity, a PCA3 score of 35 was adopted as a cutoff. It can indeed reduce unnecessary prostate biopsies by 67%, and tests for PCA3 have already been approved by the FDA to help decide whether a patient needs a prostate biopsy. Because PCA3 is related to AR-signaling pathways, the specific activity of the PCA3 promoter in PCa cells can also be used as an additional strategy for targeted therapeutic approaches. It was previously shown that the PCa-specific expression of PCA3 is mainly controlled by its promoter. Some researchers have even applied PCA3 to targeted therapy and obtained a good effect in vitro. However, even though we currently have a good understanding of the role of PCA3 in tumor genes and tissues, the picture is incomplete, and many additional studies are needed.
Written by:
Xu-Dong Yao1 and Yue Wang2 as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
1Department of Urology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, China; 2Department of Urology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China
Function of PCA3 in prostate tissue and clinical research progress on developing a PCA3 score - Abstract