赖氨酰氧化酶样蛋白4在肝细胞癌中的表达及其预后相关性分析

EXPERSSION OF LYSYL-OXIDASE LIKE 4(LOXL4)IN HEPATOCELLULAR CARCINOMA AND ITS CORRELATION WITH PROGNOSIS

利用生物信息学分析人赖氨酰氧化酶样蛋白4(1ysyl-oxidase like 4,LOXL4)基因在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及临床意义,为HCC的诊治提供新的思路。基于癌症基因图谱(the cancer genome atlas,TCGA)数据库和人类蛋白表达图谱(thehumanproteinatlas,HPA)数据库分析LOXL4在HCC组织和正常肝组织中的表达差异,分析LOXL4与HCC患者临床病理特征的相关性并进行可视化分析;通过GEPIA数据库及构建Cox回归模型分析LOXL4表达与患者预后关系;分析LOXL4与HCC肿瘤标志物基因的相关性;STRING在线数据库构建LOXL4蛋白质相互作用网络;TIMER数据库分析LOXL4基因与肿瘤免疫浸润的关系。数据库分析结果表明LOXL4在HCC中表达水平显著升高,且LOXL4表达与HCC患者的病理分级呈正相关。生存分析和Cox回归分析显示LOXL4高表达提示HCC患者预后较差。HCC中TRPV4、INHBE、ITGB5和BCL7A与LOXL4的表达呈正相关,SOD1、ADI1、HINT2和HAGH与LOXL4的表达呈负相关。LOXL4与HCC肿瘤标志物GPC3和CK19的表达呈正相关,与ARG1和CD10的表达呈负相关。LOXL4与LOX、BMP1、TLL1等10种蛋白质存在相互作用。LOXL4表达与肿瘤细胞纯度及多种免疫细胞浸润具有显著相关性。本研究揭示了LOXL4在HCC中表达上调且与HCC患者预后不良、免疫浸润及多种HCC诊断标志物密切相关,其有望成为HCC的早期筛查、诊断及预后评估的重要生物靶标。

To analyze the expression and clinical significance of humanlysyl-oxidase like 4(LOXL4)in hepatocellular carcinoma(HCC)using bioinformatics,and to provide new ideas for the diagnosis and treatment of HCC.Based on the cancer genome atlas(TCGA)database and the human protein atlas(HPA)database,the expression difference between LOXL4 in hepatocellular carcinoma(HCC)and normal liver tissues,the correlation between LOXL4 and clinicopathological characteristics of HCC patients were analyzed,and the visualization analysis was performed.The relationship between LOXL4 gene expression and patient prognosis was analyzed by GEPIA database and constructing the Cox regression model.The correlation between LOXL4 and HCC tumor marker genes was also analyzed.LOXL4 protein interaction network was constructed by STRING online database.And the relationship between LOXL4 gene and tumor immune infiltration was analyzed by TIMER database.The results of the bioinformatics analysis showed that the expression levels of LOXL4 were significantly elevated in HCC,and LOXL4 expression was positively correlated with the pathological grade of HCC patients.Survival analysis and Cox regression analysis showed that high LOXL4 expression suggested a poorer prognosis for HCC patients.In hepatocellular carcinoma,TRPV4,INHBE,ITGB5 and BCL7A were positively correlated with LOXL4 expression,and SOD1,ADI1,HINT2 and HAGH were negatively correlated with LOXL4 expression.LOXL4 was positively correlated with the expression of HCC tumor markers GPC3 and CK19,and negatively correlated with the expression of ARG1 and CD10.LOXL4 interacted with 10 proteins including LOX,BMP1,and TLL1.There was a significant correlation between LOXL4 expression and tumor cell purity and infiltration of various immune cells.The present study revealed that LOXL4 expression was upregulated in hepatocellular carcinoma and closely correlated with poor prognosis,immune infiltration and various diagnostic markers of HCC,which may be an important biological target for early screening,diagnosis and prognostic assessment of hepatocellular carcinoma.