Biological and Clinicopathological Implications of Beta-3-N-acetylglucosaminyltransferase 8 in Triple-negative Breast Cancer

Abstract

Background/Aim: Triple-negative breast cancer (TNBC) remains difficult to treat and new molecular targets are needed. Here, we investigated the impact of glycosyltransferase genes on TNBC patient survival. Patients and Methods: mRNA expression levels of 101 glycosyltransferase genes in TNBC patients were compared for correlation with patient survival using The Cancer Genome Atlas data. An antibody to β-3-Nacetylgluco-saminyltransferase 8 (B3GNT8) was applied to investigate B3GNT8 protein distribution and expression levels in 23 TNBC surgical specimens. Results: B3GNT8 mRNA levels inversely correlated with relapse-free survival (p<0.01) and overall survival (p<0.05) in TNBC patients. Anti-B3GNT8 antibody binding was observed as dots in the cytoplasm of cancer cells. These dots were supposed to correspond to B3GNT8 protein in tumour cells, but their number was smaller in relapsed patients than in non-relapsed patients. Conclusion: B3GNT8 mRNA expression levels in TNBC tumour tissues are potentially useful in distinguishing patients with favourable and poor clinical outcomes.Triple-negative breast cancer (TNBC) comprises approximately 15% of breast cancers and is defined by the lack of oestrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2) overexpression (1, 2). Because of the lack of therapeutic molecular targets, TNBC patients receive standard chemotherapy treatments, commonly anthracycline followed by taxane. However, in the adjuvant setting only about one third of TNBC patients respond to such therapy. In patients who still have residual cancer after these treatments, the prognosis is poor (3). We focused on cellular glycosylation, because it has been shown by many experimental and clinical investigations that it is involved in malignant progression and metastasis in cancer (4, 5). In breast cancer, glycosylation has been implicated in cancer cell growth and metastasis (6). Song and co-workers showed that GALNT14, a glycosyltransferase, which transfers Nacetylgalactosamine (GalNAc) to polypeptides, promotes lung-specific breast cancer metastasis (7). As an upstream event, a transcriptional activator protein, LAMTOR5, was reported to modulate GALNT1 activity in breast cancer leading to abnormal O-glycosylation (8). However, the biological and clinical significance of glycosylation in TNBC has not been previously investigated.Since glycosylation is controlled by glycosyltransferases, we conducted a comprehensive search on 101 glycosyltransferase genes in TNBC patients who did not receive neoadjuvant chemotherapy for correlation with their survival using The Cancer Genome Atlas (TCGA) mRNA expression database. From this search, β-3-N-acetylglucosaminyltransferase 8 (B3GNT8) emerged as a gene whose expression inversely correlated with the survival of TNBC patients. B3GNT8 is a 845 This article is freely accessible online.

Comprehensive prognostic and immune analysis of a glycosylation related risk model in pancreatic cancer

“…Malignant transformation is highly associated with aberrant glycosylation [ 25 ]. Previous studies have found that glycosylation-related genes are associated with the prognosis of patients with breast [ 26 ], ovarian [ 27 ], liver [ 28 ] and cervical cancer [ 29 ]. However, current studies on glycation in PC mainly focus on the influence of individual glycation type or single glycation enzyme on tumor progression [ 30 , 31 ], and there are no relevant reports on the expression status of numerous glycation related genes in PC and their relationship with PC microenvironment [ 32 ].…”