Clinical significance of the LacdiNAc‐glycosylated prostate‐specific antigen assay for prostate cancer detection

Abstract

To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc‐glycosylated prostate‐specific antigen (LDN‐PSA) and LDN‐PSA normalized by prostate volume (LDN‐PSAD). We retrospectively measured LDN‐PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop‐PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN‐PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN‐PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN‐PSA and LDN‐PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop‐PSA cohort, LDN‐PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc‐glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution (“The Study about Carbohydrate Structure Change in Urological Disease”; approval no. 2014‐195).

Glycoproteins Presenting Galactose and N-Acetylgalactosamine in Human Seminal Plasma as Potential Players Involved in Immune Modulation in the Fertilization Process

“…Involvement of PIP in immunoregulation was described in cancer and also suggested contribution to seminal plasma immunosuppresive properties [ 71 , 72 ]. Many recent reports point to the presence of an antigen called lacdiNAc (GalNAcβ1-4GlcNAc) in glycans of a KLK3 in the context of neoplastic transformation [ 73 , 74 , 75 , 76 , 77 ]. The occurrence of the above mentioned structures may be also considered in LTF.…”

Glycosylation: Rising Potential for Prostate Cancer Evaluation

“…In the cohort of prostate biopsy patients LDN-PSAD demonstrated significantly higher clinical performance to discriminate CSPC compared with LDN-PSA, PSAD, total PSA and free/total PSA ratio. The authors concluded that LacdiNAc-glycosylated PSA is significantly more efficient than the conventional PSA test in identifying patients with CSPC [111].…”

Structural Insights into the Molecular Recognition Mechanism of the Cancer and Pathogenic Epitope, LacdiNAc by Immune‐Related Lectins

“…LDN and LN were purchased from Carbosynth (OA44637 and OA08244, respectively). The 1 H-NMR resonances of LDN and LN (α/ β mixture) were completely assigned through standard 2D-TOCSY (30 and 60 ms mixing time), 2D-ROESY/2D-NOESY (500 ms mixing time) and 2D 1 H, 13 C-HSQC experiments at 298 K. Typical concentrations were 1 mM for the heteronuclear experiments in D 2 O Tris (D11)-DCl buffer solutions with pD 7.5. The resonance of 2,2,3,3tetradeutero-3-trimethylsilylpropionic acid (TSP) was used as a chemical shift reference in the 1 H-NMR experiments (δ TSP = 0 ppm).…”

“…[8] Additionally, LDN is a well-established cancer biomarker overexpressed on glycoproteins associated with several human cancers, including colon, pancreas, ovarian and prostate cancers. [9][10][11][12][13] From the recognition point of view, two human lectins, galectin-3 (hGal-3) and the macrophage galactose C-type lectin (hMGL) have previously been identified to recognize LDN epitopes. [14][15][16] In fact, either hGal-3 and hMGL were previously associated to molecular pathways that may contribute to pathogen infection [17][18][19][20] or tumour evasion of the immune system.…”

“…LDN is highly expressed in parasitic helminths such as Schistosoma mansoni [7] and was recently identified as a part of the N ‐linked glycans in the receptor binding domain of the SARS‐CoV‐2 spike protein [8] . Additionally, LDN is a well‐established cancer biomarker overexpressed on glycoproteins associated with several human cancers, including colon, pancreas, ovarian and prostate cancers [9–13] . From the recognition point of view, two human lectins, galectin‐3 (hGal‐3) and the macrophage galactose C‐type lectin (hMGL) have previously been identified to recognize LDN epitopes [14–16] .…”