ULBP1 is a prognostic biomarker associated with immune suppression in breast cancer

Breast cancer (BC) is the most common malignant tumor among women worldwide. ULBP1 (UL16 binding protein 1), as a ligand of NKG2D, has been associated with poor prognosis in multiple cancers; however, its role in BC remains unclear.

TCGA and GEO datasets (TCGA-BRCA, GSE36295, and GSE1379) were used to evaluate the expression characteristics of ULBP1 and its association with prognosis. Functional enrichment analyses were subsequently performed to identify key biological pathways. The CIBERSORT and oncoPredict algorithms were applied to assess immune infiltration features and differences in drug sensitivity, respectively. In addition, qRT-PCR, western blotting, as well as CCK-8 and Transwell assays were conducted to validate ULBP1 expression in BC cells and to examine its effects on cellular functions.

Analysis of public datasets revealed that ULBP1 is significantly overexpressed in BC tissues, and its high expression was independently associated with shortened overall survival. GSEA revealed that high ULBP1 expression was significantly enriched in immune-related pathways, including natural killer cell-mediated cytotoxicity. Immune infiltration analysis indicated that high ULBP1 expression was closely associated with neutrophil enrichment and the upregulation of multiple immune checkpoint genes. Drug sensitivity prediction showed that patients with high ULBP1 expression may be more sensitive to olaparib and other agents. In vitro experiments further confirmed that ULBP1 was highly expressed in BC cell lines, and that knockdown of ULBP1 significantly suppressed MCF-7 cell viability and reduced migratory and invasive capacities.

ULBP1 may serve as a potential novel prognostic biomarker in BC, and targeting ULBP1 may provide a new therapeutic strategy for BC.