关键词: 淋巴水肿, 差异表达基因, 基因集富集分析, 免疫调节, 生物信息学

Abstract: Objective To investigate the role of innate immune responses in acute lymphedema and their association with susceptibility to infection through a multidimensional approach integrating bioinformatics,clinical validation, and animal experiments. Methods The mouse acute lymphedema dataset GSE4333 was downloaded from the Gene Expression Omnibus （GEO）. Differentially expressed genes （DEGs） were identified using limma （|log₂FC|>1, P_adj<0.05）,and gene set enrichment analysis （GSEA） was performed with GO, KEGG, and Hallmark gene sets via clusterProfiler.Peripheral blood was collected from patients with lower-extremity lymphedema （experimental group, n=5） and healthy controls （n=5） at Traditional Chinese and Western Medicine Hospital of Wuhan （Wuhan First Hospital）（June-July 2025）.Serum levels of S100A8, S100A9, NT5E, IRF7, IFITM1, and CORO1A were measured by ELISA. A mouse tail lymphedema model was established （n=6）, and tail tissues were harvested on postoperative day 10 for qPCR analysis of the 6 target genes; LYVE-1 immunofluorescence was used to assess lymphangiogenesis. Results A total of 151 DEGs （58 upregulated,93 downregulated） were identified. GSEA revealed significant negative enrichment of the innate immune response,the regulation of inflammatory response,the chemokine signaling pathway,and the oxidative phosphorylation pathway in acute lymphedema. Clinical validation demonstrated that serum levels of S100A8,S100A9,NT5E,IRF7,IFITM1, and CORO1A were significantly lower in lymphedema patients than in healthy controls （all P<0.01）. Animal experiments confirmed that the mRNA expression levels of S100a8, S100a9, Nt5e, Irf7, Ifitm1, and Coro1a in mouse lymphedematous tail tissues were significantly downregulated （all P<0.01）. Conclusion Acute lymphedema profoundly suppresses innate immune-related signaling pathways. The systemic downregulation of key immune regulators including S100A8, S100A9, NT5E, IRF7, IFITM1, and CORO1A may represent a critical molecular basis for increased susceptibility to infection in lymphedema patients. These molecules may serve as potential biomarkers for assessing immune function and as candidate targets for immunomodulatory therapy.

Key words: lymphedema, differentially expressed genes, gene set enrichment analysis（GSEA）, immune regulation, bioinformatics