High expression of GOLM1 predicts poor prognosis and unfavorable immunotherapy efficacy in breast cancer patients

Abstract Objectives Breast cancer is a prevalent type of cancer that affects women globally, and its incidence is increasing annually. Although the differential expression of Golgi membrane protein 1 (GOLM1) has been observed in different tumors, its specific role in breast cancer remains unclear. This study aimed to determine the role and related mechanisms of GOLM1 in the development, immunotherapy, and drug sensitivity analysis of BRCA. Methods We searched databases, including TCGA, cBioPortal, UALCAN, BEST, TCIA, GSCA, etc., to investigate the relationships between GOLM1 expression and clinicopathological features, the tumor microenvironment, immunotherapy, and drug sensitivity analysis in BRCA. Single-cell sequencing data from the GSE176078 dataset were analyzed to explore the function of GOLM1 in fibroblasts, and gene ontology analyses were performed to investigate GOLM1-related pathways. Additionally, we examined the correlation between GOLM1 expression and clinicopathological features in breast cancer tissues using immunohistochemistry and multiplex immunohistochemistry. Results Increased expression of GOLM1 was linked to poorer clinical outcomes (overall survival, p=0.033) and was significantly correlated with the tumor microenvironment, particularly with macrophages and fibroblasts. Additionally, GOLM1 was associated with reduced efficacy of immunotherapy (lower IPS, TMB, NAL, and MANTIS scores in the high-GOLM1 group) and could contribute to intracellular steroid hormone receptor signaling and gland morphogenesis in patients with breast cancer. Immunohistochemistry and multiplex immunofluorescence confirmed the upregulation of GOLM1 expression in breast cancer tissues, as well as its association with immune cell infiltration and pathological grade (p=0.006). Conclusions GOLM1 may serve as a biomarker for poor prognosis and unfavorable immunotherapy efficacy in patients with breast cancer.