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.

Study of glycosylation of prostate-specific antigen secreted by cancer tissue-originated spheroids reveals new candidates for prostate cancer detection

“…Many studies have been done which focus glycans as biomarkers in prostate cancer 3 , especially N-glycan alterations of PSA [9][10][11][12]39,43,44 . Previous studies have revealed that not all patients can be detected by measuring the increase focusing only on a specific glycan structure such as α2,3-sialyl or LacdiNAc residues [9][10][11][12]43,44 . Assessing cancer-specific changes in combination with other target may improve accuracy.…”

Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer

“…It is worth comparing the clinical performance of PSA glycoprofiling in serum applied to PCa diagnostics with the performance of PSA and PHI tests. The PSA tests afford AUC ¼ 0.68 [14] and the PHI test could discriminate between PCa and BPH patients with AUC ¼ 0.74 [54]. The detection of increased levels of a-2,6-SA by the SNA lectin does not offer any advantage in terms of clinical performance (AUC ¼ 0.63) [55] over the PSA and PHI tests.…”

“…Eluted and bound fractions were collected and fPSA was detected in both fractions to calculate the a-2,3-SA percentage of PSA and a-2,6-SA percentage of PSA. The results indicate that the a-2,3-SA percentage cannot be applied to PCa diagnostics because no significant differences were observed between BPH (PSA level in the range 3.9 -14.5 ng ml 21 [54]. Out of five different Sepharose-bound lectins investigated for glycoprofiling of fPSA, MAA, in particular, was capable of distinguishing between PCa patients and BPH patients with a high statistical significance ( p , 0.001) [63].…”

“…When the sub-cohort of patients with tPSA lower than 13 ng ml 21 (28 BPH versus 39 PCa patients) was investigated using the PHI test, the AUC was 0.69 (table 1, no. 1)[54].…”

Advances in Biomarkers for PCa Diagnostics and Prognostics—A Way towards Personalized Medicine

“…Five studies present their basic research data using PCa cell lines [ 14 , 15 , 16 , 17 ] or summarize data on cancer/testis antigens (CTAs) as potential PCa biomarkers [ 18 ]. Serum markers are the subject in the vast majority of publications ( n = 8) with focus on PCa diagnostic and prognostic [ 19 , 20 , 21 , 22 , 23 ] or evaluation of advanced/metastatic disease stages [ 24 , 25 , 26 ]. Two of the four reviews further summarize biomarkers for PCa diagnostic [ 27 ] or active surveillance [ 28 ] while the other two reviews have special topics like nanoparticles as theranostic vehicles [ 29 ] or PCa stem cells [ 30 ].…”