MBOAT7在肝细胞癌中的表达及预后相关性分析

Expression and prognostic correlation analysis of MBOAT7 in hepatocellular carcinom

目的:探究膜结合的O-酰基转移酶结构域7(MBOAT7)在肝癌组织中的表达,分析MBOAT7与肝细胞癌(HCC)预后的相关性。方法:通过GEPIA在线数据库了解MBOAT7在多种肿瘤组织中的表达,利用UCSC Xena数据库下载TCGA中的HCC转录组数据,结合Cox回归分析,分析HCC中MBOAT7的表达及总体预后情况,对MBOAT7高、低表达组间的差异基因进行GO和KEGG功能富集分析,并利用GSEA软件进行基因集功能富集分析,实时荧光定量PCR(qPCR)和免疫组织化学(IHC)对肝癌组织和癌旁组织进行m RNA和蛋白质表达水平验证分析。结果:MBOAT7在多种肿瘤中具有差异表达,对TCGA的HCC转录组数据分析发现,MBOAT7在肝癌组织的表达显著高于癌旁组织(P<0.001),且与HCC预后有明显相关性(P<0.001);Cox回归结果也提示,MBOAT7和病理分级是独立预后因子(HR=2.06,95%CI:1.38~3.07,P<0.001;(HR=1.50,95%CI:1.17~1.93,P=0.002),临床性状相关分析显示,MBOAT7在年龄、体重指数(Ibm)、病理分级、家族史和肿瘤分期的亚组中表达均有显著差异(P<0.05),GO和KEGG的富集结果显示,高、低组差异基因在类固醇、高密度脂蛋白颗粒和脂蛋白颗粒等代谢中有显著富集;GSEA富集结果显示,MBOAT7高表达组在MYC信号通路、RAC1信号通路等多种癌症通路中有显著富集,qPCR和IHC实验显示,与癌旁组织相比,肝癌组织中MBOAT7基因的mRNA和蛋白质表达水平更高(P=0.006)。结论:MBOAT7的高表达可以降低HCC患者的生存率,可能通过参与脂质相关的代谢促进HCC的发展,可作为HCC的预后标志物。

Objective: To investigate the expression difference of MBOAT7 in hepatocellular carcinoma tissue and normal liver tissue, and to analyze the prognostic correlation between MBOAT7 and hepatocellular carcinoma(HCC). Methods: MBOAT7 was searched in GEPIA database to understand the expression of MBOAT7 in various tumors.The HCC transcriptome data in TCGA was downloaded from UCSC Xena database. Using Cox regression analysis, the expression of MBOAT7 in HCC and the overall prognosis were analyzed. The GO and KEGG functional enrichment analyses were performed on the differential genes between high and low MBOAT7 expression groups. Besides, functional enrichment analysis of gene set was performed using GSEA software. Real-time fluorescent quantitative PCR(qRT-PCR) and immunohistochemistry(IHC) were used to measure the mRNA and protein expression levelsof MBOAT7 in HCC tissues and paracanceroustissues, respectively. Results:MBOAT7 was differentially expressed in a variety of tumors. Analysis of the HCC transcriptome data from TCGA revealed that the expression of MBOAT7 in HCC tissues was significantly higher than that in paracancerous tissues, and it wasrelated with the prognosis of HCC patients(P<0.001). Cox regression results also suggested that MBOAT7 expression and pathological classification were independent prognostic factors for HCC(HR=2.06, 95% CI: 1.38-3.07, P<0.001;HR=1.50,95% CI:1.17-1.93,P=0.002). There was significant differencein MBOAT7 expressionamong the subgroups of different age, body mass index(Ibm),pathological classification,family history and tumor stage(P<0.05).The enrichment results of GO and KEGG showed that the differential genes in high and low MBOAT7 expressiongroups were significantly enriched in the metabolism of steroids, HDL particles, and lipoprotein particles. GSEA enrichment results showed that the MBOAT7 high-expression group was significantly enriched in many cancer pathways such as MYC signaling pathway and RAC1 signaling pathway. q RT-PCR and IHC experiments showed that compared with the paracancerous tissues, the m RNA and protein levels of MBOAT7 in HCC tissues were higher(P=0.006). Conclusion: Over-expression of MBOAT7 can reduce the survival rate of patients with HCC.MBOAT7 may promote the development of HCC through lipid metabolism,and it canserve as a prognostic marker of HCC.