甲硫氨酸代谢相关基因SLC43A2促进食管鳞状细胞癌细胞迁移和侵袭  

Methionine metabolism-related gene SLC43A2 promotes esophageal squamous carcinoma cell migration and invasion

作　　者：何敏 赵微 彭昊 王良海[1,2] HE Min;ZHAO Wei;PENG Hao;WANG Lianghai(Department of Pathology,School of Medicine Shihezi University,Shihezi 832000,China;Department of Pathology,The First Affiliated Hospital of Medicine Shihezi University,Shihezi 832000,China)

机构地区：[1]石河子大学医学院病理学系,新疆石河子832000 [2]石河子大学第一附属医院病理科,新疆石河子832000

出　　处：《中国病理生理杂志》2025年第4期669-678,共10页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.82260556);兵团指导性科技计划项目(No.2022ZD002)。

摘　　要：目的:探讨甲硫氨酸代谢相关基因在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)中的表达情况,研究甲硫氨酸和溶质载体家族43成员2(solute carrier family 43 member 2,SLC43A2)基因的表达对ESCC细胞迁移和侵袭的影响。方法:利用生物信息学分析ESCC组织与邻近正常组织的甲硫氨酸代谢关键基因的表达情况,Kaplan-Meier生存曲线分析其表达在ESCC患者预后中的价值;聚类分析揭示不同表达模式对ESCC患者总体生存期和肿瘤微环境的影响;富集分析寻找ESCC中与甲硫氨酸和SLC43A2基因紧密关联的生物学进程;免疫组织化学染色检测ESCC组织和邻近正常组织中SLC43A2蛋白的表达情况;RT-qPCR和Western blot法检测干扰ESCC细胞SLC43A2效率;Transwell实验检测甲硫氨酸限制(methionine restriction)或干扰SLC43A2后ESCC细胞迁移和侵袭能力。结果:大部分甲硫氨酸代谢相关通路中的关键酶和SLC43A2基因在ESCC肿瘤组织中高表达(P<0.05),并且这些差异基因的表达对ESCC患者的预后具有显著影响(P<0.05);聚类分析显示高表达SLC43A2基因的A簇患者预后差,肿瘤微环境中免疫细胞种类和数量显著低于B簇;富集分析显示高表达SLC43A2基因组中上皮间充质转化(epithelial-mesenchymal transition,EMT)通路信号分子显著富集(P<0.01)。此外,限制甲硫氨酸或敲减SLC43A2可抑制ESCC细胞的迁移和侵袭(P<0.01)。结论:ESCC组织中甲硫氨酸代谢活跃,SLC43A2基因在ESCC组织中高表达与患者不良预后相关,SLC43A2促进ESCC细胞迁移和侵袭。AIM:This study aimed to evaluate the expression of genes related to methionine metabolism in esophageal squamous cell carcinoma(ESCC)and investigate the effects of methionine and solute carrier family 43 member 2(SLC43A2)on the migratory and invasive abilities of ESCC cells.METHODS:Bioinformatic analysis was used to evaluate the expression of key genes related to methionine metabolism in ESCC and adjacent normal tissues.Kaplan-Meier analysis was used to assess the relationship between the expression of these genes and prognosis in patients with ESCC.Cluster analysis was used to examine the effects of methionine metabolism-related genes on overall survival and the tumor microenvironment in patients with ESCC.Enrichment analysis to search for biological processes tightly linked to methionine and SLC43A2 in ESCC.Immunohistochemical staining was used to detect the expression of the SLC43A2 protein in ESCC and adjacent normal tissues.RT-qPCR and Western blot were used to detect the interfering efficiency to SLC43A2 expression in ESCC cells.In addition,Transwell assay was used to assess the effects of methionine restriction or SLC43A2 knockdown on the migratory and invasive abilities of ESCC cells.RESULTS:Most key enzymes involved in methionine metabolism and SLC43A2 were upregulated in ESCC tissues relative to adjacent normal tissues(P<0.05).These differentially expressed genes had a significant impact on the prognosis of ESCC(P<0.05).Cluster analysis showed that patients in cluster A with high expression of SLC43A2 had a poor prognosis and that the types and numbers of immune cells in the tumor microenvironment were significantly lower in cluster A than in cluster B.Enrichment analysis showed that the high-SLC43A2-expression group was significantly enriched in the epithelial-mesenchymal transition(EMT)pathway(P<0.01).In addition,methionine restriction or SLC43A2 knockdown inhibited the migratory and invasive abilities of ESCC cells(P<0.01).CONCLUSION:Methionine metabolism is highly active in ESCC tissues,and high exp

关 键 词：食管鳞状细胞癌 甲硫氨酸代谢 预后 溶质载体家族43成员2 细胞迁移 细胞侵袭 

分 类 号：R363[医药卫生—病理学] R730.23[医药卫生—基础医学] R735.1