Emerging Biomarkers for the Diagnosis and Prognosis of Prostate Cancer

Abstract

Background: Early detection of prostate cancer (CaP), the most prevalent cancer and the second-leading cause of death in men, has proved difficult, and current detection methods are inadequate. Prostate-specific antigen (PSA) testing is a significant advance for early diagnosis of patients with CaP. Content: PSA is produced almost exclusively in the prostate, and abnormalities of this organ are frequently associated with increased serum concentrations. Because of PSA’s lack of specificity for CaP, however, many patients undergo unnecessary biopsies or treatments for benign or latent tumors, respectively. Thus, a more specific method of CaP detection is required to augment or replace screening with PSA. The focus recently has been on creating cost-effective assays for circulating protein biomarkers in the blood, but because of the heterogeneity of CaP, it has become clear that this effort will be a formidable challenge. Each marker will require proper validation to ensure clinical utility. Although much work has been done on variations of the PSA test (i.e., velocity, density, free vs bound, proisoforms) with limited usefulness, there are many emerging markers at various stages of development that show some promise for CaP diagnosis. These markers include kallikrein-related peptidase 2 (KLK2), early prostate cancer antigen (EPCA), PCA3, hepsin, prostate stem cell antigen, and α-methylacyl-CoA racemase (AMACR). We review biomarkers under investigation for the early diagnosis and management of prostate cancer. Summary: It is hoped that the use of panels of markers can improve CaP diagnosis and prognosis and help predict the therapeutic response in CaP patients.

Proteomic Profiling of Androgen-independent Prostate Cancer Cell Lines Reveals a Role for Protein S during the Development of High Grade and Castration-resistant Prostate Cancer

“…Prostate-specific antigen is the most widely used biomarker for prostate cancer. However, due to a documented lack of specificity, it may also be elevated in other non-cancerous pathologies, including benign prostate hyperplasia and prostatitis (2,3). This inevitably leads to overdiagnosis and, ultimately, to overtreatment.…”

“…The androgen receptor (AR) 3 signaling cascade has been extensively studied with respect to the progression of androgen-independent prostate cancer. Overall, AR signaling resistance has been attributed to AR gene amplifications, AR gene mutations, changes in co-regulators or steroidogenic enzymes, or alternative proteins via outlaw pathways (4 -10).…”

Comparative analysis of biological profiles of benign prostate hyperplasia and prostate cancer as potential diagnostic, prognostic and predictive indicators

“…As an organ-specific marker, it still remains a valuable indicator of processes proceeding with prostate architecture disturbances, including benign nodular hyperplasia and prostatitis. Simultaneously, PSA is still the only broadly clinically exploited monitor of the post-treatment course of prostate cancer [17].…”

“…CD44 glycoprotein performs the function of a cellular surface receptor for hyaluronic acid, a glycoaminoglycoside which takes part in cancer cell metastasizing [12]. Three forms of CD44 have been identified: full length (exons [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], standard (exons [1][2][3][4][5][16][17][18][19][20] and CD44v [13].…”

Application of omic technologies in cancer research

“…43 Multiple studies analysing the proteome of prostate cancer in comparison with healthy or benign tissue have also enabled the discovery of functional proteins altered in different disease stages. 44,45 …”