首页|ALKBH5在肝癌中的表达及其对抗肿瘤免疫的影响

ALKBH5在肝癌中的表达及其对抗肿瘤免疫的影响

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目的:探讨N6-甲基腺苷(m6A)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x2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Re-actome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.
Expression of ALKBH5 in hepatocellular carcinoma and its effect on anti-tumor immunity
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 byx2 test.The relationships between ALKBH5 and the survival of HCC patients was evaluated by Ka-plan-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 downreg-ulated 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 grade Ⅲ/Ⅳ.Patients with lower ALKBH5 showed poor overall sur-vival(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 ma-lignant progression of HCC by affecting its antitumor immunity,resulting in patient poor prognosis.

hepatocellular carcinomam6 A methylationALKBH5anti-tumor immunity

马荷花、洪雨欣、宋伟、李娟

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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

南京中医药大学鼓楼临床医学院,江苏南京 210023

肝癌 m6A甲基化 ALKBH5 抗肿瘤免疫

国家自然科学基金资助项目国家自然科学基金资助项目国家自然科学基金资助项目江苏省自然科学基金资助项目

820029843137139981803132BK20200119

2024

东南大学学报(医学版)
东南大学

东南大学学报(医学版)

CSTPCD
影响因子:1.374
ISSN:1671-6264
年,卷(期):2024.43(4)