An integrated analysis of SLC7A11 as a pan-cancer immunotherapeutic biomarker with experimental validation of its regulation by miR-148b-3p in breast cancer

BackgroundIdentifying reliable biomarkers for immunotherapy response remains challenging. Solute carrier family 7 member 11 (SLC7A11), a key regulator of redox homeostasis and ferroptosis, demonstrates significant tumor-promoting potential across cancers, yet its pan-cancer associations with immunotherapy-related features and interaction with microRNAs in triple-negative breast cancer pathogenesis remain elusive.MethodsWe systematically analyzed SLC7A11 expression across cancer types using TCGA and GTEx data, and evaluated its associations with immunotherapy-related features.

Survival analyses were assessed in general and immunotherapy-treated cohorts. A miRNA regulatory network targeting SLC7A11 was constructed in breast cancer and the SLC7A11-miR-148b-3p axis was tested via in vitro experiments in triple-negative breast cancer (TNBC) cell models (MDA-MB-231 and MDA-MB-468).ResultsPan-cancer analysis revealed upregulation of SLC7A11 transcriptional expression in over 88% tumor types, and associations with established immunotherapy-related features, including tumor mutational burden, microsatellite instability, PD-L1 expression, and immune infiltration.

Higher SLC7A11 expression was associated with improved response to immunotherapy, but inferior prognosis in most tumors, including breast cancer.