岭南现代临床外科2025，Vol.25Issue(2)：101-111,11.DOI:10.3969/j.issn.1009-976X.2025.02.004
肿瘤相关成纤维细胞分泌IGF-1调控巨噬细胞GGT5表达在食管鳞癌肿瘤微环境中的作用研究
Research on the role of cancer-associated fibroblasts-secreted IGF-1 in regulating macrophage GGT5 expression within the tumor microenvironment of esophageal squamous cell carcinoma
摘要
Abstract
Objective This research focuses on identifying a subset of macrophages that specifically and highly express the GGT5 gene.To date,there have been no reports on the GGT5+macrophage subset.Our objective is to elucidate the role of GGT5+macrophages in the progression of ESCC and the mecha-nisms regulating their expression.Methods Using TCGA,we conducted differential gene expression analysis to identify key genetic changes.Subsequently,with the aid of the TIMER database,we conducted an in-depth analysis of the relationship between GGT5 expression levels and immune cell infiltration,with a particular focus on macrophages.To further validate these analytical results,we employed immuno-histochemical and immunofluorescence techniques to visually confirm the expression of GGT5 at the sample level.Finally,through Western blotting experiments,we conducted thorough exploration and validation of the regulatory mechanisms of GGT5.Results Bioinformatics analysis revealed that GGT5 exhibits significantly high expression characteristics in ESCA,and its expression level was closely related to the activity of macrophages.Immunohistochemical and immunofluorescence experiments showed that GGT5 was specifically highly expressed mainly in M2-macrophages and its expression was also significantly increased in LNM.In the study of regulatory mechanisms,it was found that CAFs significantly regulate the expression of GGT5 in macrophages by secreting the IGF-1 cytokine,leading to a marked upregula-tion of GGT5 expression levels.Conclusion The results indicate that CAFs in the TME regulate the expression of GGT5 in macrophages by secreting the IGF-1 cytokine,thereby participating in the initiation and progression of ESCC.This discovery provides important insights for understanding the pathogenesis of ESCC and exploring new therapeutic strategies.关键词
食管鳞癌/GGT5/巨噬细胞/成纤维细胞Key words
ESCC/Gamma-Glutamyltransferase 5/macrophages/fibroblast分类
临床医学引用本文复制引用
张晓萍,李雷..肿瘤相关成纤维细胞分泌IGF-1调控巨噬细胞GGT5表达在食管鳞癌肿瘤微环境中的作用研究[J].岭南现代临床外科,2025,25(2):101-111,11.基金项目
广东省自然科学基金-面上项目(2024A1515012989) （2024A1515012989）
