Abstract
Breast cancer represents the most prevalent malignancy in women globally. While UDP-glucose pyrophosphorylase 2 (UGP2) has been implicated in tumor biology, its pathophysiological role in breast carcinogenesis remains undefined. This study systematically investigates the clinical relevance and functional mechanisms of UGP2 in breast cancer progression. Multi-omics analysis was conducted using GEPIA2, TIMER2, and TCGA databases to evaluate UGP2 expression patterns, clinicopathological correlations, and prognostic significance across breast cancer subtypes. Findings were validated through immunohistochemical analysis of 118 clinical specimens. Single-cell RNA sequencing data from GEO were employed to resolve UGP2 spatial distribution within tumor microenvironments. Functional enrichment analysis elucidated UGP2-associated pathways, while loss-of-function experiments using siRNA-mediated knockdown assessed UGP2's impact on malignant phenotypes in breast cancer cell lines. Our research found that the expression level of UGP2 in the TNBC subtype was significantly higher than that in other subtypes. The elevated expression level of UGP2 suggests a poor prognosis for breast cancer patients. The high expression level of UGP2 is positively correlated with the level of CNV. UGP2 is mainly located in epithelial cells and CAFs subsets and can participate in biological processes such as collagen synthesis. Knockdown of UGP2 in vitro can inhibit the proliferation, migration and invasion abilities of breast cancer cells. This study demonstrates that elevated UGP2 expression is clinically associated with aggressive tumor behavior and unfavorable prognosis in breast cancer patients, particularly in the triple-negative subtype (TNBC). Mechanistic analyses reveal UGP2's functional involvement in both tumor cell proliferation and stromal remodeling through cancer-associated fibroblast (CAF) interactions. The robust association between UGP2 overexpression and aggressive clinicopathological features positions it as both a promising prognostic biomarker and potential therapeutic target, particularly in TNBC management.