ALKBH5在肝癌中的表达及其对抗肿瘤免疫的影响  

Expression of ALKBH5 in hepatocellular carcinoma and its effect on anti-tumor immunity

作　　者：马荷花 洪雨欣 宋伟[1] 李娟[1] MA Hehua;HONG Yuxin;SONG Wei;LI Juan(PhaseⅠClinical Trials Center,Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University,Nanjing 210008,China;Drum Tower Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京大学医学院附属鼓楼医院Ⅰ期临床试验研究中心,江苏南京210008 [2]南京中医药大学鼓楼临床医学院,江苏南京210023

出　　处：《东南大学学报（医学版）》2024年第4期508-515,共8页Journal of Southeast University(Medical Science Edition)

基　　金：国家自然科学基金资助项目(82002984、31371399、81803132);江苏省自然科学基金资助项目(BK20200119)。

摘　　要：目的:探讨N6-甲基腺苷(m^(6)A)去甲基化酶ALKBH5在人肝癌中的表达及其对抗肿瘤免疫的影响。方法:采用免疫组织化学染色(IHC)检测50例肝细胞癌(HCC)样本中ALKBH5的表达;采用χ^(2)检验分析其与临床特征之间的关系;采用Kaplan-Meier法分析其与患者生存之间的关系;采用GSEA、GO、KEGG和Reactome通路富集分析预测ALKBH5潜在的作用机制;利用TIMER、TISIDB数据库分析ALKBH5 mRNA与免疫细胞浸润及免疫检查点分子之间的关系。结果:ALKBH5在HCC组织中低表达,并且在肿瘤直径>5 cm、有包膜浸润、ES分级Ⅲ/Ⅳ级的HCC组织中的表达更低,ALKBH5低表达组患者总生存(OS)和无进展生存(PFS)较差;基因富集分析显示ALKBH5可能参与免疫相关通路,ALKBH5与CD4^(+)T、CD8^(+)T、DC、NK等免疫细胞的浸润相关,与PD-1/L1和CTLA4的表达呈正相关。结论:ALKBH5可能通过影响抗肿瘤免疫促进肝癌恶性进展,导致患者预后不良。Objective:To investigate the expression of ALKBH5 and its effect on antitumor immunity in liver cancer.Methods:The expression of ALKBH5 in 50 patients of HCC and corresponding adjacent nontumor tissues was detected by immunohistochemical staining(IHC),and the correlations between ALKBH5 and clinical features were analyzed byχ^(2) test.The relationships between ALKBH5 and the survival of HCC patients was evaluated by Kaplan-Meier method.GSEA,GO,KEGG,and Reactome pathway enrichment analysis were applied to predict the potential mechanism of ALKBH5 involved.The relationship between ALKBH5 mRNA and immune cell infiltration and immune checkpoint molecules was analyzed in TIMER and TISIDB databases.Results:ALKBH5 was downregulated in HCC tissue,and the expression level of ALKBH5 were lower in HCC tissues with tumor size>5 cm,or with infiltration of tumor encapsulation,or ES gradeⅢ/Ⅳ.Patients with lower ALKBH5 showed poor overall survival(OS)and progression free survival(PFS).Moreover,gene enrichment analysis showed that ALKBH5 might participate in immune related pathways.ALKBH5 was correlated with the infiltration of immune cells,such as CD4^(+)T,CD8^(+)T,DC,NK,and the expression of PD-1/L1 and CTLA4.Conclusion:ALKBH5 can promote malignant progression of HCC by affecting its antitumor immunity,resulting in patient poor prognosis.

关 键 词：肝癌 m^(6)A甲基化 ALKBH5 抗肿瘤免疫 

分 类 号：R735.7[医药卫生—肿瘤] R657.3[医药卫生—临床医学]