Abstract
OBJECTIVE: Pancreatic cancer is distinguished by its high likelihood of metastasis and drug resistance, while the fundamental mechanisms are inadequately elucidated. This study aimed to identify pivotal hub genes associated with pancreatic cancer and assess their potential utility in predicting its onset and progression. METHODS: Weighted gene co-expression network analysis (WGCNA) combined with differential expression analysis identified novel susceptibility modules and hub genes for pancreatic cancer. Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses were utilized to explore the potential roles of these hub genes. Receiver operator characteristic curves and nomogram models were developed to evaluate diagnostic efficacy. Mendelian randomization, flow cytometry, Transwell, and RNA sequencing were conducted to explore the association between C-X-C motif chemokine ligand 10 (CXCL10) and immune infiltration. RESULTS: WGCNA analysis was performed to build gene co-expression networks, and ten key genes were found. CXCL10 was the central gene, and its expression was significantly linked to the survival of patients with pancreatic cancer and their response to immune checkpoint inhibitors. CXCL10 demonstrated the ability to stimulate the differentiation of macrophages toward the M2 phenotype. CXCL10 could facilitate the metastasis of pancreatic cancer cells by modulating macrophage polarization. CXCL10 affects macrophage polarization by regulating the expression of vascular endothelial growth factor A. CONCLUSIONS: CXCL10 demonstrates potential as a therapeutic target for managing pancreatic cancer.