Role of SLC31A1 in prognosis and immune infiltration in breast cancer: a novel insight

Objective: Copper, an essential metal element for humans, plays vital functions in cancer prognosis and immunity. SLC31A1, a high-affinity copper transporter, helps regulate copper homeostasis and has been implicated in tumor prognosis through mechanisms such as drug resistance, autophagy, ferroptosis, and cuproptosis. However, the role of SLC31A1 in breast cancer (BRCA) and its association with tumor immune infiltration has not been fully elucidated. This study aimed to investigate the expression pattern of SLC31A1, its clinical significance, and its effect on tumor immune infiltration in BRCA.

Methods: We comprehensively analyzed multiple datasets, including Gene Expression Profiling Interaction Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), UALCAN, and Kaplan-Meier (KM) plotter, to assess the expression of SLC31A1 and its prognostic value in BRCA. Additionally, TIMER and TISIDB were used to explore the correlation between SLC31A1 expression and the extent of tumor immune infiltration.

Results: SLC31A1 was significantly upregulated in BRCA tissues compared to adjacent non-tumor tissues. Higher SLC31A1 expression levels were associated with poorer clinical outcome. Multivariate Cox regression analysis confirmed that SLC31A1 served as an independent prognostic indicator. Furthermore, SLC31A1 expression showed significant associations with various immunomodulators, chemokines, chemokine receptors, and tumor-infiltrating lymphocytes (TILs), including CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), follicular helper T cells (Tfh), neutrophils, M2 macrophages, tumor-associated macrophages (TAMs), and monocytes. These findings suggest that SLC31A1 may regulate macrophage polarization and T cell exhaustion in BRCA, contributing to immune evasion and poor prognosis.

Conclusion: Our study underscores the importance of further research to explore the therapeutic potential of targeting SLC31A1 and to uncover its additional roles in BRCA beyond the known mechanisms of drug resistance, autophagy, ferroptosis, and cuproptosis.