ADAMTS14在肾透明细胞癌中的表达和作用机制

Expression and mechanism of action of ADAMTS14 in clear cell renal cell carcinoma

目的基于生物信息学分析Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶14(ADAMTS14)在肾透明细胞癌(ccRCC)中的表达和作用机制。方法通过TIMER、TCGA、ICGC、GEPIA和Kaplan-Meier Plotter数据库分析ADAMTS14在ccRCC中的表达、预后价值、临床意义和作用机制。结果泛癌分析结果显示,与正常组织相比,ADAMTS14在包括ccRCC在内的多种恶性肿瘤中显著高表达。分析TCGA和ICGC数据库的转录数据发现,ADAMTS14在ccRCC组织中显著高表达。Kaplan-Meier生存曲线显示,ADAMTS14高表达与患者的预后较差有关。临床病理相关性分析结果显示,ADAMTS14表达上调与患者较高的临床分期、组织学分级和TNM分期有关。单变量和多变量Cox分析结果显示,ADAMTS14高表达是ccRCC患者总体生存率较低的独立预后因素。功能分析结果显示,高低表达组之间的差异表达基因主要富集在细胞外基质及其受体的相互作用、细胞因子及其受体的相互作用、PI3K-Akt信号通路和IL-17信号通路。结论ADAMTS14在ccRCC组织中高表达,且与患者的临床不良结局相关,可作为ccRCC的潜在生物标记物。

Objective To analyze the expression and mechanism of action of ADAM metallopeptidase with thrombospondin type 1 motif 14(ADAMTS14)in clear cell renal cell carcinoma(ccRCC)based on bioinformatics.Methods The expression,prognostic value,clinical significance and mechanism of action of ADAMTS14 in ccRCC were analyzed by TIMER,TCGA,ICGC,GEPIA and Kaplan-Meier Plotter databases.Results The results of pan-cancer analysis showed that ADAMTS14 was significantly highly expressed in a variety of malignancies,including ccRCC,compared with the normal tissues.Analysis of transcriptional data from TCGA and ICGA databases revealed that ADAMTS14 was significantly highly expressed in ccRCC tissues.Kaplan-Meier survival curves showed that the high expression of ADAMTS14 was associated with a poorer prognosis of patients.The results of clinicopathological correlation analysis showed that the up-regulation of ADAMTS14 expression was associated with the higher clinical stage,histological grade and TNM stage in patients.The results of univariate and multivariate Cox analyses showed that the high expression of ADAMTS14 was an independent prognostic factor for lower overall survival in patients with ccRCC.The results of functional analysis showed that the differentially expressed genes between the high and low expression groups were mainly enriched in the interaction between extracellular matrix and its receptors,the interaction between cytokines and its receptors,the PI3K-Akt signaling pathway,and the IL-17 signaling pathway.Conclusion ADAMTS14 is highly expressed in ccRCC tissues and is associated with poor clinical outcome of patients,which can be used as a potential biomarker for ccRCC.