GALNT1 Expression Is Associated with Angiogenesis and Is a Prognostic Biomarker for Breast Cancer in Adolescents and Young Adults (AYA)

SIMPLE SUMMARY: Breast cancer (BC) in adolescents and young adults (AYA) has unique biological qualities, but the details of these features remain unclear, and treatment options are comparable to those of other age groups. In this study, we identified a gene that demonstrates a strong association with patient prognosis solely in AYA patients, despite the fact that its expression does not differ by age group. Although this gene, GALNT1, has no prognostic significance in whole BC, when examined in AYA BC, high GALNT1 was significantly associated with worse survival. Furthermore, high GALNT1 expression was found to be an independent factor for survival among several clinical features of AYA patients. Finally, high GALNT1 BC is associated with increased EMT, angiogenesis, and protein secretion in AYA patients, but not in the elderly. We report the clinical relevance of the GALNT1 gene in AYA BC. ABSTRACT: It is well established that genetic information differs amongst the adolescent and young adult population (AYA) and older patients. Although several studies on genetic information have been conducted, no current prognostic biomarker exists to help differentiate survival outcomes amongst AYA patients. The GALNT family of genes have been associated with several cancer etiologies, such as the Tn antigen and epithelial-mesenchymal transition (EMT); however, the clinical significance of GALNT1 expression in breast cancer (BC) remains unclear. We investigated the clinical relevance of GALNT1 expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highest GALNT1 expression compared to ER-positive/HER2-negative BC, GALNT1 levels in BC were not associated with clinical aggressiveness, including histological grade, AJCC stage and N-category, and patient survival, consistently in both the METABRIC and GSE96058 cohorts. There was also no biological difference between low- and high-GALNT1 expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found in GALNT1 expression levels among AYAs and older patients. However, high GALNT1 expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, high GALNT1 expression was found to be an independent factor among several clinical features, including subtype, histological grade, AJCC T and N-category, in AYA patients. In both cohorts, BC with high GALNT1 expression demonstrated low levels of CD8(+) T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels of GALNT1 BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate that GALNT1 expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients.