【摘要】 目的 基于生物信息学分析醛缩酶B在肝细胞癌中的表达水平及临床意义。方法 从癌症基因组图谱数据库下载肝细胞癌组织和正常肝脏组织的RNA测序数据，利用人类蛋白质表达图谱数据库和R软件分析醛缩酶B蛋白和mRNA在肝细胞癌组织和正常肝脏组织中的表达情况。利用STRING数据库对与醛缩酶B直接相互作用的蛋白进行蛋白-蛋白相互作用(PPI)分析，并对编码上述蛋白的基因进行基因本体论(GO)功能富集分析、京都基因与基因组百科全书(KEGG)通路富集分析。分析醛缩酶B mRNA表达量与肝细胞癌患者临床病理特征的相关性，采用COX回归模型分析肝细胞癌患者预后的危险因素，绘制受试者工作特征(ROC)曲线分析醛缩酶B mRNA表达量预测肝细胞癌患者预后的效能。结果 醛缩酶B蛋白和mRNA在肝细胞癌组织中均呈低表达。PPI分析结果显示，醛缩酶B与二羟基丙酮激酶、果糖1,6-二磷酸酶1、果糖1,6-二磷酸酶2等10个蛋白直接相互作用。GO功能富集分析和KEGG通路富集分析结果显示，与醛缩酶B直接相互作用的蛋白参与的生物过程以单糖代谢过程、己糖代谢过程、果糖1,6-二磷酸代谢过程为主，细胞组分以转移酶复合物-转移含磷基团为主，分子功能以单糖结合、碳水化合物激酶活性、单磷酸腺苷结合为主，参与的信号通路富集在糖酵解/糖异生、碳代谢、果糖和甘露糖代谢等方面。不同TNM分期、病理学分期、组织学分级、血清甲胎蛋白含量的肝细胞癌患者之间醛缩酶B mRNA表达量差异均具有统计学意义(均P<0.05)。生存曲线显示，醛缩酶B mRNA低表达的肝细胞癌患者中位生存期短于高表达者(P<0.05);COX回归模型分析结果显示，醛缩酶B mRNA表达量是影响肝细胞癌患者预后的独立危险因素(P<0.05);ROC曲线显示，醛缩酶B mRNA表达量预测肝细胞癌患者预后具有一定的准确性(曲线下面积为0.818),特异度为88.0%,灵敏度为73.3%。结论 醛缩酶B蛋白及mRNA在肝细胞癌组织中呈低表达，醛缩酶B mRNA表达量与肝细胞癌患者的临床病理特征和预后密切相关，醛缩酶B mRNA低表达者的肿瘤恶性程度更高，且预后更差。醛缩酶B有可能成为诊断肝细胞癌及判断患者预后的新型分子标志物。更多还原

【Abstract】 Objective To analyze the expression and clinical significance of aldolase B in hepatocellular carcinoma based on bioinformatics. Methods RNA sequencing data of hepatocellular carcinoma tissues and normal hepatic tissues were downloaded from the database of the Cancer Genome Atlas, and the protein and mRNA expressions of aldolase B in hepatocellular carcinoma tissues and normal hepatic tissues were analyzed by the application of the Human Protein Atlas database and R software. Analysis of protein-protein interaction(PPI) was performed on proteins directly interacting with aldolase B by STRING database, and Gene Oncology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the genes encoding the aforesaid proteins. The correlation of mRNA expression of aldolase B with clinicopathologic features of patients with hepatocellular carcinoma was analyzed. The risk factors for prognosis in patients with hepatocellular carcinoma were analyzed by using COX regression model. The efficiency of mRNA expression of aldolase B in predicting prognosis of patients with hepatocellular carcinoma was analyzed by drawing receiver operating characteristic(ROC) curve. Results The protein and mRNA expressions of aldolase B was low-expressed in hepatocellular carcinoma. The results of PPI analysis revealed that aldolase B directly interacted with 10 proteins with respect to dihydroxyacetone kinase, fructose 1, 6-bisphosphatase 1, and fructose 1, 6-bisphosphatase 2, etc. The results of GO functional enrichment analysis and KEGG pathway enrichment analysis indicated that the proteins directly interacting with aldolase B were mainly involved in the metabolic processes of monosaccharide, hexose and fructose 1, 6-bisphosphatase, in the cellular components of transferase complex-transferring phosphorus containing groups, and in the molecular functions of monosaccharide binding, carbohydrate kinase activity, and adenosine monophosphate binding, as well as in the signaling pathways enriched in the perspectives of glycolysis/gluconeogenesis, carbon metabolism, fructose and mannose metabolism, etc. There was statistically significant difference in aldolase B mRNA expression between hepatocellular carcinoma patients with different TNM stages, pathologic classifications, histological grades, and serum alpha-fetoprotein contents(all P<0.05). The survival curve implied that the median survival time of hepatocellular carcinoma patients with a low mRNA expression of aldolase B was shorter than that with a high mRNA expression of aldolase B(P<0.05). The results of COX regression analysis interpreted that aldolase B mRNA expression was the independent risk factor affecting prognosis in patients with hepatocellular carcinoma(P<0.05). ROC curve showed that aldolase B mRNA expression in predicting prognosis in patients with hepatocellular carcinoma exerted an accuracy to a certain extent(the area under the curve was 0.818), the specificity was 88.0%, and the sensitivity was 73.3%. Conclusion The protein and mRNA expressions of aldolase B in hepatocellular carcinoma tissues is low. The mRNA expression of aldolase B is closely related to the clinicopathological features and prognosis of patients with hepatocellular carcinoma. Patients with a low mRNA expression of aldolase B have a higher degree of malignant carcinoma and a worse prognosis. Aldolase B may become a novel molecular marker for diagnosing hepatocellular carcinoma and prognosis judgement of patients.更多还原