Altered Glycosylation of PSA in Prostate Cancer Tissue.

Background: The glycosylation of proteins is commonly altered in cancer. This offers novel opportunities for cancer biomarker development. As prostate-specific antigen (PSA) is a glycoprotein, identification of cancer-specific PSA-glycoforms is feasible. Such PSA-glycoforms may provide valuable diagnostic and prognostic information.

Methods: PSA-glycoforms were studied in tissues, using in situ proximity-ligation assay (PLA)-based detection with a PSA-specific antibody and 25 different glycan-binding lectins.

Results: Using 25 different lectins and a small tissue microarray (TMA), we showed that glycosylation of PSA in cancerous tissues is different from that in benign prostate. In a larger TMA with samples from 162 patients, PSA-glycoforms detected by succinylated wheat germ (WGA_succ) and Vicia villosa (VVA) lectins were enriched in cancerous tissues as compared to adjacent benign tissues from the same patients (p < 10^-4 for both, Kruskal-Wallis H test), although strong total PSA staining was more often found in benign tissues (p = 6*10^-14).

Conclusions: We showed here that glycosylation of PSA is changed in situ in prostate cancer. The identified lectins, showing preferential binding to cancer-associated PSA-glycoforms, will aid the future development of a diagnostic serum test of prostate cancer. Such a test has potential to revolutionize prostate cancer diagnostics.