Polypeptide-GalNAc-Transferase-13 Shows Prognostic Impact in Breast Cancer.

Abstract

Simple SummaryThe knowledge of the molecular mechanisms underlying breast tumorigenesis has allowed the identification of an increasing number of biomarkers, which have been correlated with cancer prognosis or used as predictors for specific treatment responses, thus improving the ability to individualize therapy. Protein O-glycosylation is dysregulated in breast cancer cells. Abnormal O-glycans have functional importance in cell adhesion, invasion, and metastasis. Polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family enzymes regulate the initial steps of mucin type O-glycosylation and may be responsible for the altered glycosylation observed in cancer. Previous reports have related GalNAc-T13 expression to cancer aggressiveness. In the present work, we produced a specific monoclonal antibody against GalNAc-T13 which is capable of recognizing this enzyme on formalin-fixed tissues. We observed a significant higher expression of this enzyme in metastatic samples compared with the corresponding primary tumors. Significantly, a high GalNAc-T13 score was associated with worse patient survival rates, thus supporting its prognostic potential.Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients’ clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.