Integrated Multi-Omics Profiling of Young Breast Cancer Patients Reveals a Correlation between Galactose Metabolism Pathway and Poor Disease-Free Survival

Abstract

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to intermediate and elderly patients. Therefore, it is imperative to identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify the prognostic factotrs. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, the galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that the galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between the galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.