唾液酸化IgG在肺腺癌中高表达并促进肺腺癌增殖和迁移  

Sialylated IgG is highly expressed in lung adenocarcinoma(LUAD)and promotes proliferation and migration of LUAD in mice

作　　者：葛舒童 王诗杰 朱广迎 GE Shu-tong;WANG Shi-jie;ZHU Guang-ying(Department of Radiation Oncology,Peking University China-Japan Friendship School of Clinical Medicine,Beijing 100029,China)

机构地区：[1]北京大学中日友好临床医学院放射肿瘤科,北京100029 [2]中国医学科学院北京协和医学院,北京100730 [3]中日友好医院国家呼吸医学中心放射肿瘤科,北京100029

出　　处：《中日友好医院学报》2024年第3期148-153,F0003,共7页Journal of China-Japan Friendship Hospital

基　　金：中日友好医院人才引进科研启动基金项目(No.2016-RC-4)。

摘　　要：目的:探究唾液酸化IgG(SIA-IgG)在肺腺癌(LUAD)中的表达和功能,以及抗SIA-IgG抗体(RP215抗体)对小鼠体内Lewis肺腺癌生长和肿瘤微环境的影响。方法:应用癌症基因组图谱(TCGA)数据库对IgG重链γ恒定区(IGHG)基因进行泛癌分析;用Kaplan-MeierPlotter数据库分析IGHG基因表达与肺腺癌患者预后的关系。克隆形成实验和迁移实验分别评估沉默SIA-IgG后肺腺癌细胞的增殖和迁移能力的变化。采用LLC细胞在雌性C57BL/6小鼠(6周龄)体内成瘤并给予RP215抗体治疗,观察小鼠体内肿瘤的生长状况,流式分析观察RP215治疗对肿瘤微环境的影响。结果:泛癌分析,IgG在肺腺癌中表达上调(P<0.01)且与患者的不良预后呈正相关。小鼠实验,沉默SIA-IgG的表达后,肺腺癌细胞的增殖和迁移能力受到明显抑制(均P<0.01)。RP215抗体治疗可明显抑制小鼠体内Lewis肺腺癌的生长(P<0.05),且小鼠肿瘤微环境中的巨噬细胞和中性粒细胞比例降低(P<0.05)。结论:SIA-IgG或可作为肺腺癌的潜在治疗靶点。Objective:To investigate the expression and function of sialylated IgG(SIA-IgG)in LUAD,and the effect of anti-SIA-IgG antibody(RP215 antibody)on the growth and tumor microenvironment of Lewis LUAD in mice.Methods:Pan-cancer analysis of immunoglobulin heavy constant gamma(IGHG)genes was performed using The Cancer Genome Atlas(TCGA)database.The relationship between gene expression of IGHG and survival prognosis of LUAD patients was analyzed using the Kaplan-Meier Plotter database.The expression of SIA-IgG in LUAD PC9 cells was silenced using shRNA,and the knockdown efficiency of SIA-IgG was detected by Western blot.Subsequently,clone formation assays and migration assays were utilized to evaluate the proliferation and migration capabilities of LUAD cells.Then,LLC cells were used to form tumors in female C57BL/6 mice(six weeks)and treated with RP215 antibody.The growth of tumors in the mice was observed,and the effect of RP215 treatment on tumor microenvironment was observed by flow cytometry.Results:IgG expression is upregulated in LUAD(P<0.01)and correlates with poor prognosis.Silencing SIA-IgG expression significantly inhibits the proliferation(P<0.01)and migration(P<0.01)capabilities of LUAD cells.Subsequently,treatment with RP215 antibody markedly suppresses Lewis LUAD growth in mice(P<0.05),and the proportion of macrophages and neutrophils in the tumor microenvironment of mice was reduced after RP215 treatment(P<0.05).Conclusion:SIA-IgG may serve as a potential therapeutic target for LUAD.

关 键 词：肺腺癌 唾液酸化免疫球蛋白G 增殖 迁移 

分 类 号：R734.2[医药卫生—肿瘤]