YY1/GOLGA8B调控轴在肝细胞癌进展中的表达意义及潜在分子机制  

The Expression Significance and Potential Molecular Mechanism of YY1/GOLGA8B Regulatory Axis in the Progression of Hepatocellular Carcinoma

作　　者：李建棣 殷彬烔 邓玉龙 何融泉 詹彦婷 陈罡[1] 党裔武[1] LI Jiandi;YIN Bintong;DENG Yulong(Department of Pathology,the First Affiliated Hospital of Guangxi Medical University,Nanning City,Guangxi Zhuang Autonomous Region 530021)

机构地区：[1]广西医科大学第一附属医院病理科,广西壮族自治区南宁市530021 [2]广西医科大学第一附属医院肿瘤内科,广西壮族自治区南宁市530021

出　　处：《医学理论与实践》2024年第19期3249-3255,3275,共8页The Journal of Medical Theory and Practice

基　　金：广西研究生教育创新计划项目(YCSW2023220,JGY2023068);广西教育科学“十四五”规划2022年度高校创新创业教育专项课题重点课题(2022ZJY2791);广西医科大学本科教育教学改革项目(2023Z10);广西壮族自治区卫生健康委员会科研课题(Z-A20220469);国家级大学生创新创业训练计划(202210598043X);广西医科大学未来学术之星基金(WLXSZX23111)

摘　　要：目的:探讨Golgin A8家族成员B(GOLGA8B)在肝细胞癌中的临床病理学意义及潜在分子功能。方法:利用免疫组织化学染色评估GOLGA8B蛋白在肝细胞癌、非癌对照组织的相对表达水平及其区分能力。基于全球基因芯片及高通量测序数据,探究GOLGA8B的mRNA综合表达水平,鉴定肝细胞癌过表达基因和GOLGA8B共表达基因,对其交集基因进行功能注释。本研究利用染色质免疫共沉淀测序分析,预测了阴阳1转录因子(YY1)对GOLGA8B的特异性调控机制,并从组织、单细胞层面验证YY1转录因子的表达水平及与GOLGA8B的Spearman相关性。根据TIMER反卷积算法探究GOLGA8B及YY1转录因子与免疫微环境的关联。结果:GOLGA8B蛋白在肝细胞癌组织呈强阳性表达(285例肝细胞癌VS 89例非癌对照,P<0.001),对肝细胞癌具有较强区分能力(曲线下面积=0.997)。基于2151例非癌对照肝组织、3091例肝细胞癌组织、26个不同平台,GOLGA8B的过表达在mRNA层面得到验证(标准平均差=0.26,95%可信区间:0.12~0.41)。537个GOLGA8B共表达基因在表观遗传调控信号中显著富集;其中,染色质免疫共沉淀测序分析结果提示GOLGA8B受YY1转录因子正性调控。全球基因芯片、高通量测序分析结果支持YY1在肝细胞癌组织显著高表达(SMD=0.29,95%可信区间:0.14~0.45)且与GOLGA8B表达水平呈显著正相关(P<0.05)。单细胞测序结果亦证实YY1/GOLGA8B在肝细胞癌恶性上皮细胞亚群内过表达。YY1与肝细胞癌免疫微环境显著正相关。结论:YY1/GOLGA8B轴可能在肝细胞癌中发挥促癌作用。Objective:To investigate the clinicopathological significance and potential molecular function of Golgin A8 family member B(GOLGA8B)in hepatocellular carcinoma(HCC).Methods:Immunohistochemical staining was used to evaluate the relative expression level of GOLGA8B protein in HCC and non-cancerous control tissues and its discriminatory ability.Based on the global gene chip and high-throughput sequencing data,the comprehensive mRNA expression level of GOLGA8B was explored,the overexpressed genes of HCC and the co-expressed genes of GOLGA8B were identified,and the intersection genes were functionally annotated.In this study,chromatin immunoprecipitation sequencing analysis was used to predict the specific regulatory mechanism of Yin Yang 1(YY1)on GOLGA8B,and the expression level of YY1 transcription factor and its Spearman correlation with GOLGA8B were verified from the tissue and single cell levels.The relationship between GOLGA8B and YY1 transcription factors and immune microenvironment was explored according to the TIMER deconvolution algorithm.Results:GOLGA8B protein was strongly expressed in HCC tissues(285 cases of HCC VS 89 cases of non-cancerous controls,P<0.001),and had a strong ability to distinguish HCC from normal liver(area under the curve=0.997).Based on 2151 non-cancer control liver tissues,3091 HCC tissues,and 26 different platforms,the overexpression of GOLGA8B was verified at the mRNA level[standard mean difference=0.26,95%confidence interval(95%CI):0.12~0.41].A total of 537 GOLGA8B co-expressed genes were significantly enriched in epigenetic regulation signals.Among them,the results of chromatin immunoprecipitation sequencing analysis suggested that GOLGA8B was positively regulated by YY1 transcription factor.The results of global gene chip and high-throughput sequencing analysis support that YY1 is highly expressed in HCC tissues(SMD=0.29,95%CI:0.14~0.45)and positively correlated with GOLGA8B expression level(P<0.05).Single cell sequencing results also confirmed that YY1/GOLGA8B was overexpressed

关 键 词：肝细胞癌 免疫组织化学 YY1/GOLGA8B调控轴 分子机制 

分 类 号：R73-3[医药卫生—肿瘤]