| Summary: | 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 <i>GALNT1</i> expression in breast cancer (BC) remains unclear. We investigated the clinical relevance of <i>GALNT1</i> expression in BC using two large independent cohorts. We found that, although triple-negative BC (TNBC) had the highest <i>GALNT1</i> expression compared to ER-positive/HER2-negative BC, <i>GALNT1</i> 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-<i>GALNT1</i> expression BC, as analyzed by hallmark gene sets via gene set enrichment analysis (GSEA). Further, no significant difference was found in <i>GALNT1</i> expression levels among AYAs and older patients. However, high <i>GALNT1</i> expression was associated with significantly worse survival in AYA patients, in both cohorts. Furthermore, high <i>GALNT1</i> 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 <i>GALNT1</i> expression demonstrated low levels of CD8<sup>+</sup> T-cell infiltration, but not other anti-cancerous or pro-cancerous immune cells. Finally, high levels of <i>GALNT1</i> BC demonstrated increased EMT, angiogenesis, and protein secretion in the AYA population, but not in older patients. In conclusion, our findings demonstrate that <i>GALNT1</i> expression was found to be associated with angiogenesis and EMT, and may have potential as prognostic biomarker, specifically in AYA patients.
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