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, 22 (2), 214-221

Recent Progress and Perspectives on Prostate Cancer Biomarkers


Recent Progress and Perspectives on Prostate Cancer Biomarkers

Shingo Hatakeyama et al. Int J Clin Oncol.


The application of prostate-specific antigen (PSA) in prostate cancer (PC) screening, diagnosis, and prognosis has improved the clinical management of PC patients. However, the PSA assay has been faced with criticism due to its potential association with over-diagnosis and subsequent overtreatment of patients with indolent disease. The United States Preventive Services Task Force incited much debate over PSA-based screening in 2012 by recommending against this approach. However, the PSA assay remains the first-line tool for the early detection of PC. This debate highlights the unmet need for non-invasive PC biomarkers with greater sensitivity and specificity that are capable of distinguishing aggressive disease from indolent disease, predicting treatment response, and guiding treatment decisions. Recent investigations into putative PC biomarkers have focused on PSA isoform assays (prostate health index, 4-kallikurein panel), PC-associated genes in the urine (PCA3 and TMPRSS2-ERG), glycan-associated biomarkers (S2, 3PSA, GCNT1, and tri- and tetra-antennary serum N-glycans), and circulating tumor cells. Although substantial efforts to identify novel PC biomarkers that might replace PSA have been put forth, the majority of the putative PC biomarkers reported in the last few years are still under investigation or validation. This review provides an overview of the current state of PC biomarker research and focuses on a few promising PC biomarkers in development.

Keywords: Biomarker; PCA3; PHI; PSA; Prostate cancer; S2,3PSA.

Conflict of interest statement

The authors declare no potential conflicts of interest.


Fig. 1
Fig. 1
PSA synthesis and PSA isoforms. PSA synthesis begins with the cleavage of the proenzyme PSA (proPSA) leader sequence from preproPSA. There are several truncated isoforms of proPSA, including [−7]proPSA, [−5]proPSA, and [−2]proPSA. [−2]proPSA is the predominant proPSA isoform in tumor extracts, indicating that it has the potential to play a role in the early detection of PC and the prediction of aggressive disease. The cleavage of the propeptide in proPSA by human kallikrein 2 (hk2) generates the mature PSA molecule. Benign PSA (BPSA), intact PSA, and [−2]proPSA exist as free PSA molecules in the serum. cPSA complexed PSA
Fig. 2
Fig. 2
Aberrant glycosylation of PSA N-glycans (S2, 3PSA) in PC. In healthy patients, the terminal sialic acid of PSA is predominantly α2,6-linked to galactose residues. In patients with PC, the terminal sialic acid is predominantly α2,3-linked to galactose residues
Fig. 3
Fig. 3
Overview of potential prostate cancer biomarkers. Novel biomarkers were classified according to screening to prognostic phase based on types of biomaterials. Asterisk US FDA approved, N/A not available

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