Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection

Abstract

Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors. For that, new diagnostic methods are being developed, such as PCA-3, PSA isoforms that have resulted in the 4K score or the Prostate Health Index (PHI), and PSA glycoforms. In the present study, we have compared the PHI with our recently developed PSA glycoform assay, based on the determination of the α2,3-sialic acid percentage of serum PSA (% α2,3-SA), in a cohort of 79 patients, which include 50 PCa of different grades and 29 benign prostate hyperplasia (BPH) patients. The % α2,3-SA could distinguish high-risk PCa patients from the rest of patients better than the PHI (area under the curve (AUC) of 0.971 vs. 0.840), although the PHI correlated better with the Gleason score than the % α2,3-SA. The combination of both markers increased the AUC up to 0.985 resulting in 100% sensitivity and 94.7% specificity to differentiate high-risk PCa from the other low and intermediate-risk PCa and BPH patients. These results suggest that both serum markers complement each other and offer an improved diagnostic tool to identify high-risk PCa, which is an important requirement for guiding treatment decisions.

Keywords: PHI; diagnosis; glycosylation; proPSA; prostate cancer; prostate specific antigen; α2,3-sialic acid.

Figure 1

α2,3-SA percentage of Prostate Specific Antigen (PSA) (% α2,3-SA) of the cohort of 79 serum samples. Benign Prostate Hyperplasia (BPH) samples are represented with an open circle (ο), low risk PCa with a cross (×), intermediate risk PCa with a filled triangle (▲) and high risk PCa with a filled circle (●). (A) Representation of % α2,3-SA against tPSA serum levels; dotted line (---) shows the cutoff value for discriminating high risk PCa samples from the other three groups; (B) Representation of % α2,3-SA against the pathology. The center line indicates the median, and the top and bottom lines, the 75th and 25th percentiles, respectively; (C) Representation of the Receiver operating characteristic (ROC) curves for % α2,3-SA, tPSA, and %fPSA; (D) Correlation plot of % α2,3-SA from the PCa serum samples with their Gleason score. The mean of % α2,3-SA of each Gleason score is shown with a horizontal line (-).

Figure 2

Prostate Health Index (PHI) values of the cohort of 79 serum samples. BPH samples are represented with an open circle (ο), low risk PCa with a cross (×), intermediate risk PCa with a filled triangle (▲) and high risk PCa with a filled circle (●). (A) Representation of PHI value against tPSA serum levels; dotted line (---) shows the cutoff value for discriminating high risk PCa samples from the other three groups; (B) Representation of PHI value against the pathology. The center line indicates the median, and the top and bottom lines, the 75th and 25th percentiles, respectively; (C) Representation of the ROC curves for the PHI value, tPSA and %fPSA (D) Correlation plot of PHI value of the PCa samples with their Gleason score. The mean PHI value of each Gleason score is shown with a horizontal line (-).

Figure 3

% α2,3-SA and PHI combination of the cohort of 79 serum samples. BPH samples are represented with an open circle (ο), low risk PCa with a cross (×), intermediate risk PCa with a filled triangle (▲) and high risk PCa with a filled circle (●). (A) Representation of % α2,3-SA and PHI combination values against the pathology. The center line indicates the median, and the top and bottom lines, the 75th and 25th percentiles, respectively; dotted line (---) shows the cutoff value for discriminating high risk PCa samples from the other three groups; (B) Correlation plot of % α2,3-SA and PHI combination of the PCa samples with their Gleason score. The mean % α2,3-SA and PHI combination value of each Gleason score is shown with a horizontal line (-); (C) ROC curves for the diagnosis of high-risk PCa versus low- and intermediate-risk PCa and BPH. Diagnostic performance of % α2,3-SA and PHI combination (solid line) compared with PHI (dotted line) and % α2,3-SA (dashed line).