摘要
脑特异性血管生成抑制剂1相关蛋白2样2(brain-specific angiogenesis inhibitor 1-associated protein 2-like 2,BAIAP2L2)是一种上皮特异性BAR结构域蛋白,近年来被发现在多种肿瘤中高表达,然而在肝癌中的角色尚不清楚。本文通过生物信息学方法,探讨了BAIAP2L2在肝癌中的表达、生物学意义及潜在的临床应用价值,旨在为BAIAP2L2作为肝癌的新型标志物提供理论依据。文中首先从TCGA和ICGC数据库下载肝癌m RNA-seq、mi RNA-seq、DNA甲基化数据及临床病理资料,从HPA数据库获取蛋白质表达数据,以比较癌组织和癌旁组织中BAIAP2L2的表达差异,分析BAIAP2L2表达与肝癌临床病理特征的关系。随后,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估BAIAP2L2表达水平在肝癌诊断中的性能,通过绘制生存曲线比较不同BAIAP2L2表达组患者的生存差异,并利用Cox回归计算风险比(hazard ratio,HR)。最后,利用mi RWalk数据库预测BAIAP2L2的潜在调控因子,采用TIMER数据库分析BAIAP2L2表达与肝癌组织中浸润免疫细胞的相关性,借助基因集富集分析(gene set enrichment analysis,GSEA)探讨BAIAP2L2涉及的功能通路。结果显示:BAIAP2L2在肝癌组织中的表达水平显著高于癌旁组织(P<0.001),对肝癌具有较好的诊断价值(AUC=0.891,P<0.001),且BAIAP2L2的表达水平与患者性别、T分期、甲胎蛋白(alpha fetoprotein,AFP)、临床分期和存活状态均显著相关(P<0.05);BAIAP2L2高表达患者预后更差(P<0.05),且BAIAP2L2是肝癌患者独立预后的危险因素(HR:1.522,95%CI:1.044~2.219,P<0.05);BAIAP2L2甲基化与其表达水平呈显著负相关(P<0.001),且BAIAP2L2低甲基化患者的预后更差(P<0.05);hsa-miR-99a-3p是一个可以调控BAIAP2L2表达的因子;BAIAP2L2表达与肝癌组织中B细胞、CD4~+T细胞、CD8~+T细胞、巨噬细胞、中性粒细胞和树突细胞的浸润水平均显著相关(P<0.05);BAIAP2L2在肝癌中参与调节细胞周期、p53信号�
Brain-specific angiogenesis inhibitor 1-associated protein 2-like 2(BAIAP2L2)is an epithelialspecific BAR domain protein.It was recently reported that BAIAP2L2 was overexpressed in multiple cancer tissues,but its roles in liver cancer are still poorly understood.To provide theoretical basis for BAIAP2L2 as a new liver cancer biomarker,this study explored the expression level of BAIAP2L2 in liver cancer and its biological significance and potential clinical application value through bioinformatics methods.Firstly,mRNAseq,miRNA-seq,DNA methylation data and corresponding clinicopathologic information of liver cancer patients were downloaded from the TCGA and ICGC databases,and protein expression data were obtained from the HPA database.The expression levels of BAIAP2L2 in cancer and adjacent tissues were compared,and the relationship between the expression of BAIAP2L2 and the clinicopathological characteristics of liver cancer was analyzed.Subsequently,the receiver operating characteristic(ROC)curve was used to evaluate the performance of BAIAP2L2 expression in the diagnosis of liver cancer.The survival curves were drawn to compare the differences in groups of patients with different expression levels of BAIAP2L2,and Cox regression analysis was used to calculate the hazard ratio(HR).Finally,the potential regulatory factors for BAIAP2L2 were predicted in the miRWalk database.The TIMER database was used to explore the correlation between BAIAP2L2 expression and infiltrated immune cells in liver cancer tissues.Gene set enrichment analysis(GSEA)was performed to identify BAIAP2L2 involved functional pathways.The results showed that the expression level of BAIAP2L2 in liver cancer tissues was significantly higher than that in adjacent tissues(P<0.001),and BAIAP2L2 had a good diagnostic value for liver cancer(AUC=0.891,P<0.001).Its expression level was significantly correlated with the gender,T stage,alpha fetoprotein(AFP),clinical stage and survival status in liver cancer patients(P<0.05).Patients with high expression of
作者
屈才浩
马腾达
王瑞
李晓梅
李玉民
QU Cai-hao;MA Teng-da;WANG Rui;LI Xiao-mei;LI Yu-min(Department of General Surgery,the Second Hospital of Lanzhou University,Lanzhou 730030,Gansu,China;Key Laboratory of Digestive System Tumors of Gansu Province,Lanzhou 730030,Gansu,China)
出处
《生命科学研究》
CAS
CSCD
2022年第5期441-451,共11页
Life Science Research
基金
甘肃省国际科技合作项目(18YF1WA113)
甘肃省科技重大专项(20ZD7FA003)。
