Role of BTLA in ovarian cancer and its clinical prognostic significance based on multi-omics analysis

BACKGROUND: Ovarian cancer (OV) is a highly lethal gynecological malignancy with limited effective biomarkers for prognosis and precision immunotherapy. B and T lymphocyte attenuator (BTLA) is an immune checkpoint molecule involved in tumor immune regulation, but its role in OV remains unclear. METHODS: Transcriptomic data from The Cancer Genome Atlas (TCGA) were analyzed to evaluate BTLA expression and its potential clinical relevance in OV. Exploratory multivariable Cox regression analysis was performed to examine the association between BTLA expression and patient prognosis. Functional characteristics were investigated through gene set enrichment and variation analyses, protein-protein interaction analysis, and regulatory network construction. Single-cell RNA sequencing (ScRNA-seq) was applied to explore cellular heterogeneity and BTLA-related cell-cell communication. Drug sensitivity analyses and molecular docking were conducted to assess therapeutic relevance. Experimental assays were performed to validate BTLA expression. RESULTS: BTLA was significantly upregulated in OV tissues compared with normal controls. Higher BTLA expression was associated with patient prognosis in exploratory Cox regression and Kaplan-Meier (KM) analyses. Functional enrichment revealed associations with immune- and tumor-related pathways including epithelial mesenchymal transition (EMT), interleukin-10 signaling, and interferon responses. Single-cell analysis demonstrated BTLA-related transcriptional heterogeneity across cell populations, with epithelial cells showing the highest activity. Drug sensitivity profiling identified differential responses between BTLA expression groups, and molecular docking suggested moderate binding affinity between BTLA and genistein (Vina score = - 6.3 kcal/mol). Experimental validation confirmed increased BTLA expression at both mRNA and protein levels in OV tissues. CONCLUSION: These findings suggest that BTLA may be involved in the tumor immune microenvironment of OV and may provide preliminary clues as a potential biomarker and therapeutic target.