Wu Xiaochao, Rong Longfei, Tang Ruiyi, Li Quanpeng, Wang Fei, Deng Xueting, Miao Lin
Department of Gastroenterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of General Surgery, SIR RUN RUN Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Open Med (Wars). 2025 Mar 21;20(1):20241117. doi: 10.1515/med-2024-1117. eCollection 2025.
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.
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.
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.
CXCL10 demonstrates potential as a therapeutic target for managing pancreatic cancer.
胰腺癌以其高转移可能性和耐药性为特征，而其基本机制尚未得到充分阐明。本研究旨在确定与胰腺癌相关的关键枢纽基因，并评估它们在预测胰腺癌发病和进展方面的潜在效用。
加权基因共表达网络分析（WGCNA）结合差异表达分析，确定了胰腺癌新的易感模块和枢纽基因。利用京都基因与基因组百科全书和基因本体分析来探索这些枢纽基因的潜在作用。绘制受试者工作特征曲线和列线图模型以评估诊断效能。进行孟德尔随机化、流式细胞术、Transwell实验和RNA测序，以探索C-X-C基序趋化因子配体10（CXCL10）与免疫浸润之间的关联。
进行WGCNA分析以构建基因共表达网络，发现了10个关键基因。CXCL10是核心基因，其表达与胰腺癌患者的生存率及其对免疫检查点抑制剂的反应显著相关。CXCL10表现出刺激巨噬细胞向M2表型分化的能力。CXCL10可通过调节巨噬细胞极化促进胰腺癌细胞的转移。CXCL10通过调节血管内皮生长因子A的表达影响巨噬细胞极化。
CXCL10显示出作为治疗胰腺癌的潜在靶点的可能性。
