基于生物信息学分析ASPH在预测肺腺癌预后中的价值及机制研究

The value and mechanism of ASPH in predicting the prognosis of lung adenocarcinoma based on bioinformatics

目的:探讨天冬氨酸β-羟化酶(ASPH)在肺腺癌中的表达情况、预后价值和在癌症中的作用机制。方法:使用Oncomine、GEPIA和TIMER数据库分析ASPH在肿瘤组织和正常组织中的表达差异,并用HPA数据库在蛋白水平验证,推测其临床意义。应用Kaplan-Meier plotter及GEPIA探讨ASPH表达水平与肺腺癌患者总生存时间的关系,提取Oncomine数据库中患者的生存信息加以整理分析,绘制生存曲线,研究ASPH表达水平与预后的关系。绘制ASPH蛋白互作网络,并进行功能富集分析,研究其作用机制。结果:来自Oncomine、GEPIA和TIMER数据库的数据均表示ASPH在肺腺癌组织中显著高表达(P<0.05),GEPIA数据库还证明了ASPH与肺腺癌患者病理分期显著相关。分析Oncomine数据表明,ASPH表达升高肺腺癌患者的生存时间更短(HR=0.39,95%CI:0.17~0.88,P=0.0240),GEPIA及Kaplan-Meier plotter分析结果均支持ASPH高表达预示着肺腺癌患者预后更差(P=2.4E-08)。ASPH及相关基因功能涉及钙离子调控及缺氧反应,并参与Notch、mTOR信号通路,影响肿瘤的发生与发展。ASPH还与免疫细胞浸润及相关标志物呈现弱相关性。结论:ASPH在肺腺癌组织中表达明显升高,预示着患者预后不良,且参与多条与癌症相关的信号通路,与免疫细胞浸润呈现弱相关性,ASPH可能是肺腺癌新的预后和潜在治疗标志物。

Objective:To investigate the expression,prognostic value and mechanism of Aspartyl/Asparaginyl beta-hydroxylase(ASPH)in lung adenocarcinoma(LUAD).Methods:Oncomine,GEPIA and TIMER database were used to analyze the difference of ASPH expression in tumor tissues and normal tissues,and the HPA database was used to verify the protein level to speculate its clinical significance.Kaplan-Meier plotter and GEPIA were used to explore the relationship between ASPH expression level and the overall survival time of LUAD patients.The survival information of patients in Oncomine database was extracted and analyzed,and survival curves were drawn to study the relationship between ASPH expression level and prognosis.The ASPH protein-protein interaction network was drawn,and functional enrichment analysis was performed to study its mechanism of action.Results:The data from Oncomine,GEPIA and TIMER database showed that ASPH was highly expressed in LUAD tissues(P<0.05).The GEPIA database also proved that ASPH was significantly related to the pathological stage of patients with LUAD.The analysis of Oncomine data showed that the survival time of LUAD patients with increased ASPH expression was shorter(HR=0.39,95%CI:0.17~0.88,P=0.0240),and the results of GEPIA and Kaplan-Meier plotter all supported that the high expression of ASPH predicted poor prognosis of LUAD patients(P=2.4E-08).The functions of ASPH and related genes involved calcium ion regulation and hypoxic response,and participated in Notch and mTOR signaling pathways,affecting occurrence and development of tumors.There was also a weak correlation between ASPH and immune infiltrating cells and related markers.Conclusion:The expression of ASPH in LUAD tissues is significantly increased,and it indicates the poor prognosis and participates in multiple cancer-related signaling pathways.ASPH may be a new prognosis and potential therapeutic target for LUAD.