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.
近年来，年轻乳腺癌患者的发病率显著上升，与中老年患者相比，其生存结局更差且具有独特的临床特征。因此，识别年轻患者特有的临床特征至关重要，这可能为潜在治疗策略的制定和生存结局的改善提供重要线索。本研究通过对大规模临床队列的转录组与基因组数据进行整合分析，确定了影响预后的关键因素。同时，结合单细胞转录组数据分析及体外实验验证，我们发现年轻患者具有更高的肿瘤分级、更差的无病生存期（DFS）、更高的TP53与BRCA1基因突变频率、更低的PIK3CA突变频率，以及八条代谢通路的显著上调。其中，半乳糖代谢通路在年轻患者中异常活跃，且与不良DFS显著相关。进一步分析与实验表明，该通路可能通过调控肿瘤细胞的干性特征，最终导致患者生存结局恶化。综上所述，本研究系统揭示了年轻乳腺癌患者独特的临床病理学、转录组学及基因组学特征，并首次阐明半乳糖代谢通路与肿瘤干性及不良无病生存期之间的内在关联。
肿瘤(癌症)患者之家