DNA损伤修复基因FANCI与肝癌预后和免疫浸润相关性  

Correlation of DNA Damage Repair Gene FANCI with Prognosis and Immune Infiltration of Hepatocellular Carcinoma

作　　者：游莹 梅美华 谭宁歆 陈怡丽[2] 池沛冬[3] 何晓顺[1] 黄俊琪 YOU Ying;MEI Mei-hua;TAN Ning-xin;CHEN Yi-li;CHI Pei-dong;HE Xiao-shun;HUANG Jun-qi(Organ Tr ansplant Center,The First Affiliated Hospital,Sun Yat-sen University//Guangdong Provincial Key Laborato-ry of Organ Donation and Transplant Immunology,The First Affiliated Hospital,Sun Yat-sen University//Guangdong Pro-vincial International Cooperation Base of Science and Technology,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China;Department of Laboratory Medicine,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China;Department of Laboratory Medicine,Sun Yat-sen University Cancer Center,Guangzhou 510060,China)

机构地区：[1]中山大学附属第一医院器官移植科//广东省器官捐献与移植免疫重点科实验室//广东省器官移植国际科技合作基地,广东广州510080 [2]中山大学附属第一医院检验科,广东广州510080 [3]中山大学肿瘤防治中心检验科,广东广州510060

出　　处：《中山大学学报（医学科学版）》2023年第1期51-62,共12页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81871238);广东省器官捐献与移植免疫重点实验室建设项目(2020B1212060026);广东省器官移植国际合作基地建设项目(2015B050501002,2020A0505020003);广东省自然科学基金(2021A1515010435);广州市科技计划项目(202103000007)。

摘　　要：【目的】探究DNA损伤修复基因FANCI在肝癌中的表达水平,及其与预后、临床分期、免疫浸润的关系。【方法】在本研究中,使用TCGA、GTEx、TIMER2.0及qRT-PCR法、蛋白质印迹法和免疫组织化学法研究FANCI在肝癌中的表达及其与不同临床分期之间的相关性;使用Kaplan-Meier Plotter数据库分析FANCI与肝癌预后的关系;使用TISIDB数据库探索FANCI与肝癌免疫细胞浸润及免疫检查点的关系;使用STRING数据库探索FANCI相结合的蛋白;使用TCGA及GTEx数据库进行GO及KEGG富集分析;通过细胞实验探索了FANCI在肝癌中的作用。【结果】与正常组织相比,肝癌组织FANCI的mRNA和蛋白表达水平上调(P<0.001);高表达FANCI的肝癌患者预后较差(P<0.001);肝癌组织中FANCI的表达与组织活化的CD4+T细胞数目、Th2细胞数目及免疫检查点基因的表达呈正相关,且FANCI高表达组的B细胞及巨噬细胞浸润水平明显较低(P<0.01);GO及KEGG富集分析显示FANCI相关基因富集在氨基酸跨膜转运体活性等多种生物过程中;细胞实验发现敲低FANCI后,肝癌的增殖、侵袭及迁移能力下降(P<0.05)。【结论】FANCI在肝癌组织中高表达,可能起抑制抗肿瘤免疫的作用,并作用于氨基酸跨膜转运等通路,与不良预后相关,敲低FANCI后,肝癌的增殖、侵袭及迁移能力得到抑制。【Objective】 To evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma(HCC) and its relationship with prognosis, clinical stage and immune infiltration.【Methods】 In this study, TCGA, GTEx, TIMER2.0, HPA database and qRT-PCR, western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages;Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC;the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC;the STRING database was used to detect the protein binding with FANCI;the TCGA and GTEx databases were used for GO and KEGG enrichment analysis;Cell experiments were used to explore the role of FANCI in HCC.【Results】 Compared with normal tissues, the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated(P<0.001);and HCC patients with high expression of FANCI had poor prognosis(P<0.001);the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4+ T cells, the number of Th2 cells and the expression of immune checkpoints, and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group(P<0.01);GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity;Cell experiments showed that knockdown of FANCI could inhibit the proliferation, invasion and migration of HCC(P<0.05).【Conclusions】 FANCI is highly expressed in hepatocellular carcinoma tissues, which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport, and is associated with poor prognosis. The proliferation, invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

关 键 词：Fanconi贫血补充组Ⅰ 肝癌 免疫浸润 免疫检查点 

分 类 号：R73[医药卫生—肿瘤]