胃癌三级淋巴结构ARHGAP12表达分析OA
Analysis of ARHGAP12 expression in tertiary lymphoid structures of gastric cancer
目的:探究胃癌三级淋巴结构(tertiary lymphatic structures,TLS)区域内Rho GTP酶激活蛋白12(Rho GTPase activating protein 12,ARHGAP12)表达水平及对肿瘤免疫反应的影响.方法:通过TCGA数据库分析胃腺癌(n=414)与正常胃组织(n=211)中ARHGAP12 mRNA表达差异.免疫印迹法检测12例胃腺癌及癌旁组织中ARHGAP12蛋白表达水平.采用多重免疫荧光检测胃癌组织切片TLS和肿瘤引流淋巴结(tumor-draining lymph node,TDLN)中ARHGAP12蛋白表达.Hallmark及KEGG信号通路富集分析ARHGAP12 mRNA表达与免疫相关通路活化的相关性.采用免疫组化检测28例胃癌患者肿瘤组织切片中ARHGAP12蛋白表达水平,并结合临床数据分析细胞因子表达水平与ARHGAP12免疫组化染色评分的相关性.KM plotter数据库分析胃癌患者ARHGAP12 mRNA水平与预后的关系.结果:TCGA数据库分析结果显示,胃癌组织中ARHGAP12 mRNA表达较正常胃组织显著升高(P＜0.001).免疫印迹结果显示,胃腺癌及癌旁组织样本中ARHGAP12蛋白相对表达水平无统计学差异(P＞0.05).多重免疫荧光结果显示,ARHGAP12蛋白在胃癌细胞、TLS和TDLN区域呈高表达(P＜0.05).Hallmark及KEGG信号通路富集分析结果提示,ARHGAP12 mRNA表达参与干扰素应答途径的激活及抗原呈递过程.此外,ARHGAP12免疫组化染色高评分与胃癌患者术前血清中IFN-γ水平呈正相关(P＜0.05).胃癌组织中ARHGAP12 mRNA高表达与总生存时间长呈正相关(P＜0.05).结论:ARHGAP12在胃癌TLS中呈高表达,且其与干扰素-γ相关抗肿瘤免疫途径活化呈正相关.
Objective:To investigate the expression levels of Rho GTPase-activating protein 12(ARHGAP12)within tertiary lymphoid structures(TLS)in gastric cancer and its impact on tumor immune response.Methods:ARHGAP12 mRNA expression differences between gastric cancer(n=414)and normal tissues(n=211)were analyzed using TCGA databases.Western blotting was employed to validate the protein expression levels of ARHGAP12 in 12 pairs of gastric cancer and adjacent tissue samples.Immunofluorescence was used to detect ARHGAP12 protein expression in TLS and tumor-draining lymph nodes(TDLN)in gastric tissue pathological sections.Hallmark and KEGG pathway enrichment analyses were conducted to assess the correlation between ARHGAP12 mRNA expression and the activation of immune-related pathways.Immunohistochemical staining was performed to examine the protein expression levels of ARHGAP12 in pathological sections of tumor tissues from 28 gastric cancer patients,and clinical data were analyzed to explore the correlation between cytokine expression levels and ARHGAP12 immunohistochemical staining scores.KM plotter database was used to analyze the relationship between ARHGAP12 mRNA expression and prognosis of patients with gastric cancer.Results:TCGA database analysis showed that ARHGAP12 mRNA expression in gastric cancer tissues was significantly higher than that in adjacent tissues(P＜0.001).Western blotting results indicated that there was no significant difference in ARHGAP12 protein expression levels between the gastric adenocarcinoma and adjacent tissue samples(P＞0.05).Multiplex immunofluorescence results demonstrated higher expression of ARHGAP12 protein in gastric cancer cells,TLS,and TDLN regions(P＜0.05).Hallmark and KEGG pathway enrichment analysis suggested that ARHGAP12 mRNA expression is involved in the activation of interferon response pathways and antigen presentation processes.Furthermore,high ARHGAP12 immunohistochemical staining score was positively correlated with preoperative serum IFN-γlevels in patients with gastric cancer(P＜0.05).KM plotter database analysis showed that high expression of ARHGAP12 mRNA in gastric cancer tissues is positively correlated with longer overall survival period(P＜0.05).Conclusion;ARHGAP12 is highly expressed in gastric cancer TLS,and it is positively correlated with the activation of interferon-γ-related anti-tumor immune pathways.
季湧;朱伟;高峰;陈诗涵;徐晓凤;吕剑;龙聪;蔡圣强;徐传奇;陈静;朱淼琳
靖江市人民医院普外科,江苏靖江 214500江苏大学医学院,江苏镇江 212013靖江市人民医院普外科,江苏靖江 214500江苏大学医学院,江苏镇江 212013靖江市人民医院检验科,江苏靖江 214500靖江市人民医院普外科,江苏靖江 214500靖江市人民医院检验科,江苏靖江 214500靖江市人民医院普外科,江苏靖江 214500靖江市人民医院普外科,江苏靖江 214500靖江市人民医院普外科,江苏靖江 214500江苏省肿瘤医院病理科,江苏南京 210009
医药卫生
胃癌Rho GTP酶激活蛋白12(ARHGAP12)三级淋巴结构干扰素反应肿瘤引流淋巴结
gastric cancerRho GTPase-activating protein 12(ARHGAP12)tertiary lymphatic structuresinterferon responsetumor-draining lymph nodes
《江苏大学学报（医学版）》 2026 (1)
30-35,43,7
江苏省卫生健康委员会医学科研项目(No.X373)
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