A multidimensional pan-cancer analysis of CD47 and its role in promoting malignant phenotype in pancreatic adenocarcinoma.

[BACKGROUND] CD47 is a widely expressed member of the immunoglobulin superfamily and plays important roles in cell proliferation, adhesion, and immune evasion. Previous studies have shown that CD47 contributes to tumor development by inhibiting immune-mediated clearance in multiple cancer types. However, the expression patterns of CD47 across different malignancies, its prognostic relevance, and its associations with the tumor immune microenvironment remain incompletely elucidated in a pan-cancer context.

[METHODS] In this study, we performed a comprehensive pan-cancer analysis using publicly available multi-omics datasets to examine CD47 expression patterns, clinical relevance, and immune features across 34 tumor types, together with their associations with patient prognosis, genomic instability indicators, tumor microenvironment composition, and biomarkers relevant to immunotherapy.

[RESULTS] The results showed that high CD47 expression was associated with unfavorable survival outcomes in multiple cancers and was significantly correlated with immune microenvironment characteristics and several immunotherapy-related biomarkers, although notable heterogeneity was observed among different tumor types. Based on the pan-cancer screening results, pancreatic adenocarcinoma was selected for further investigation. In pancreatic adenocarcinoma, CD47 was significantly upregulated and associated with higher histological grade and increased macrophage infiltration. In vitro experiments confirmed that CD47 knockdown reduces pancreatic cancer cell proliferation, migration, and invasion. In addition, in co-culture systems, treatment with RRx-001 was associated with enhanced macrophage phagocytic activity and altered expression of macrophage-related markers.

[CONCLUSIONS] In conclusion, this study systematically characterizes the clinical and immunological associations of CD47 across multiple cancers and highlights its potential role in pancreatic adenocarcinoma, supporting the further investigation of CD47 as a therapeutic target.