基于生物信息学分析HHAT的表达在前列腺癌中的作用及机制探索

The role of HHAT expression in prostate cancer

目的探索Hedgehog酰基转移酶(HHAT)表达在前列腺癌(PCa)中的诊断、预后价值,以及在PCa中发挥作用的信号通路。方法从癌症基因组图谱(TCGA)数据库中获取PCa组织及正常组织的HHAT表达数据,比较组间基因表达差异,并利用基因表达(GEO)数据库中的数据进行验证,评估PCa中HHAT表达的诊断及预后价值,同时分析临床特征与HHAT表达之间的相关性以及分析其是否为PCa预后指标的影响因素,通过基因集富集分析(GSEA)探索HHAT在PCa中可能参与的信号通路。结果相对于配对前列腺组织及非配对前列腺组织,HHAT在PCa组织中低表达(P<0.05)。在PCa患者中,HHAT在高T分期组、N1组、>60岁组、Gleason评分>7分组以及疾病未缓解组显著低表达,HHAT的表达能够有效区分正常组织与肿瘤组织[受试者工作特征曲线下面积(AUC)=0.753],HHAT低表达的患者具有较差的无疾病进展生存期(PFI)(P<0.05),高T分期、高Gleason评分以及HHAT的低表达是PCa较差PFI的独立危险因素(P<0.05),HHAT在PCa中可能与氨基酸及其衍生物的代谢信号通路和M期信号通路有关。结论HHAT的表达在PCa中具有较高的诊断、预后价值,并可能通过肿瘤相关信号通路发挥作用。

Objective To explore the diagnostic and prognostic value of the expression of hedgehog acyltransferase(HHAT)in prostate cancer(PCa),and the possible signaling pathways that HHAT take part in.Methods HHAT expression data of PCa and normal tissues were obtained from TCGA database,and the difference of gene expression among groups was compared.The data in the GEO database for verification were used,and the diagnostic and prognostic value of HHAT expression in PCa were evaluated.The association between clinical characteristics and HHAT expression was analyzed,and the influencing factors of prognosis were analyzed.The signal pathway that HHAT may participate in was explored by GSEA analysis.Results HHAT was significantly down-regulated in PCa compared with matched and unmatched normal tissues(P<0.05),and HHAT was significantly down-regulated in high T stage group,N group,group>60 years old group,Gleason>7 group and disease not alleviated groups.HHAT expression could effectively distinguish normal tissue from tumor tissues(AUC=0.753),and patients with low HHAT expression had poor progression-free interval(PFI)(P<0.05).High T stage,high Gleason score,and low HHAT expression were independent risk factors of poor PFI in PCa(P<0.05).HHAT may participate in metabolism of amino acids and derivatives and M phase signaling pathways.Conclusions HHAT expression has a high diagnostic and prognostic value in PCa,and may play a role in tumor related signaling pathway.