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

BACKGROUND: 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. METHODS: 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. RESULTS: The fPSAMGLglycovariant 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 fPSAMGLGV was independent of prostate gland volume. Using a logistic regression analysis the fPSAMGLGV significantly improved on the four-kallikrein model. CONCLUSIONS: Due to Eu-nanoparticles and a dense fPSA capture spot, the fPSAMGL glycovariant identifies an fPSA subform with the highest cancer specificity compared to the four conventional kallikreins.

Identification of stemness-related glycosylation changes in head and neck squamous cell carcinoma.

BACKGROUND: Altered glycosylation is a hallmark of cancer associated with therapy resistance and tumor behavior. In this study, we investigated the glycosylation profile of stemness-related proteins OCT4, CIP2A, MET, and LIMA1 in HNSCC tumors. METHODS: Tumor, adjacent normal tissue, and blood samples of 25 patients were collected together with clinical details. After tissue processing, lectin-based glycovariant screens were performed. RESULTS: Strong correlation between glycosylation profiles of all four stemness-related proteins was observed in tumor tissue, whereas glycosylation in tumor tissue, adjacent normal tissue, and serum was differential. CONCLUSIONS: A mannose- and galactose-rich glycosylation niche associated with stemness-related proteins was identified.