癌睾丸抗原ACRBP与肝癌免疫浸润的初探  

Preliminary Study on the Relationship between Cancer Testis Antigen ACRBP and Immune Infiltration of Liver Cancer

作　　者：曾曌月 赵振凯 蒋佳男 李枫 农蔚霞[1] 葛盈盈 谢小薰[1,2] 张庆梅 罗彬[1,2] ZENG Zhaoyue;ZHAO Zhenkai;JIANG Jianan(Department of Histology and Embryology,Guangxi Medical University,Guangxi 530021,China)

机构地区：[1]广西医科大学组织学与胚胎学教研室,南宁530021 [2]广西高校区域性疾病基础研究重点实验室,南宁530021

出　　处：《医学研究杂志》2025年第1期79-86,共8页Journal of Medical Research

基　　金：广西自然科学基金资助项目(2018GXNSFAA281251,2023GXNSFAA026120)。

摘　　要：目的 探究癌-睾丸抗原顶体素结合蛋白(acrosin binding protein,ACRBP)在肝癌中的表达及其与免疫浸润的相关性。方法 首先利用UALCAN(university of alabama at birmingham cancer data analysis portal,UALCAN)和HPA(human protein atlas,HPA)数据库分析肝癌和正常肝组织中ACRBP的mRNA和蛋白的表达情况。基于TCGA数据,采用TIMER(tumor immune estimation resource,TIMER)数据库、CIBERSOFT(cell-type identification by estimating relative subsets of rna transcripts,CIBERSORT)工具和TISIDB(an integrated repository portal for tumor-immune system interactions,TISIDB)数据库分析肝癌中ACRBP的表达与免疫细胞浸润及免疫调节基因的相关性。此外,还分离人外周血单个核细胞(peripheral blood mononuclear cell,PBMC),与ACRBP表达下调的肝癌细胞共培养,通过ELISA(enzyme linked immunosorbent assay,ELISA)检测免疫分子的分泌,流式细胞术检测PBMC的凋亡情况。结果 生物信息学分析显示,在肝癌组织中,ACRBP mRNA及蛋白表达均显著高于正常肝组织;ACRBP的mRNA表达与调节性T细胞(Treg细胞)浸润、免疫抑制分子和趋化因子等多种免疫调节基因呈正相关;与正常肝组织比较,ACRBP高表达的肝癌组织中浆细胞,γδT细胞,自然杀伤细胞(NK细胞)和M2型巨噬细胞浸润比例明显减少。在体外试验中,下调肝癌细胞中ACRBP的表达,发现PBMC分泌α肿瘤坏死因子、γ干扰素和白细胞介素2增加,PBMC的凋亡率有所增多。结论 肝癌中ACRBP的表达与免疫细胞浸润相关,ACRBP参与免疫细胞调节而影响肿瘤微环境,为将来开发以ACRBP为靶标的免疫治疗提供了理论基础。Objective To explore the expression of cancer-testis antigen ACRBP in liver cancer and its correlation with immune infiltration.Methods Firstly,UALCAN and HPA databases were used to analyze the expression of ACRBP mRNA and protein both in liver cancer and normal liver tissues.The correlation between the expression of ACRBP in liver cancer and immune cell infiltration,and immune regulation genes were analyzed based on TCGA data,TIMER database,CIBERSOFT tool and TISIDB database.Then,human peripheral blood mononuclear cells(PBMC) were isolated and co-cultured with liver cancer cells with down-regulated ACRBP expression.The secretion of immune molecules was measured by ELISA,and the apoptosis of PBMC was detected by flow cytometry.Results Bioinformatics analysis revealed that the expression of ACRBP mRNA and protein in liver cancer tissues was significantly higher than those in normal liver tissues.The expression of ACRBP mRNA was positively correlated with Treg cell infiltration,immunosuppressive molecules,chemokines and other immunoregulatory genes.Compared with normal liver tissues,liver cancer tissues with high expression of ACRBP was significantly reduced in the infiltration of Plasma cells,γδT cells,NK cells and M2macrophages.In vitro,by down-regulateing the expression of ACRBP in liver cancer cells,the secretion of TNF-α,IFN-γ and IL-2 was increased,and the apoptosis of PBMC was also increased.Conclusion The expression of ACRBP in live cancer is associated with the infiltration of immune cells.ACRBP participates in the regulation of immune cells and influences the tumor microenvironment,laying the foundation for the future development of immunotherapy targeting ACRBP.

关 键 词：肝癌 ACRBP 癌睾丸抗原 免疫浸润 

分 类 号：R392.12[医药卫生—免疫学]