Tumor-associated macrophages positive for SPP1 indicate a poorer clinical prognosis in pancreatic ductal adenocarcinoma

Objective: Pancreatic ductal adenocarcinoma (PDAC) presents a significant clinical challenge due to its poor prognosis and limited treatment modalities. The tumor microenvironment (TME), particularly tumor-associated macrophages (TAMs), is known to critically influence PDAC progression. This study aims to identify a specific subtype of TAM promoting tumor progression. Methods: We utilized single-cell sequencing data to identify macrophages highly correlated with patient prognosis. Subsequently, through weighted gene co-expression network analysis (WGCNA), we pinpointed the upregulated expression of secreted phosphoprotein 1 (SPP1). Following this, we analyzed the potential mechanisms by which SPP1+ macrophages contribute to tumor progression through cellular communication and transcriptomic sequencing. Results: Through single-cell RNA sequencing (scRNA-seq), our study identified a specific subset of TAMs with high expression of SPP1, which is strongly correlated with reduced survival in PDAC patients. Conclusions: These TAMs with elevated SPP1 expression may function as a potential prognostic biomarker for identifying patients with aggressive disease.