Lectin-nanoparticle concept for free PSA glycovariant providing superior cancer specificity

Using lectins to target cancer-associated modifications of PSA glycostructure for identification of clinically significant prostate cancers, e.g., Gleason score (GS) ≥ 7, from benign and indolent cancers (GS 6), is highly promising yet technically challenging. From previous findings to quantify increased PSA fucosylation in urine, we set out to construct a robust, specific test concept suitable for plasma samples.

Macrophage galactose-binding lectin (MGL) coupled to 100 nm Eu3 + -nanoparticles was used to probe PSA captured from cancer cell lines, seminal plasma, and plasma samples from 249 patients with a clinical suspicion of prostate cancer onto 3 mm dense spots of free PSA antibody fab fragments. Results were compared to four kallikrein tests: tPSA, fPSA, iPSA and hK2.

The fPSA^MGLglycovariant provided superior discrimination of the GS ≥ 7 and benign + GS 6 groups (p 0.0003) compared to fPSA (NS). The corresponding AUC in ROC analysis was 0.70 compared to 0.66 for tPSA. In contrast to all four kallikrein tests, the fPSA^MGLGV was independent of prostate gland volume. Using a logistic regression analysis the fPSA^MGLGV significantly improved on the four-kallikrein model.

Due to Eu-nanoparticles and a dense fPSA capture spot, the fPSA^MGL glycovariant identifies an fPSA subform with the highest cancer specificity compared to the four conventional kallikreins.