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含G结构域和FHA结构域的血管生成因子1(AGGF1 )作为肝细胞癌(HCC)的诊断生物标志物和不良预后因素:来自生物信息学分析的证据

Angiogenic Factor with G Patch and FHA Domains 1 (AGGF1) Acts as Diagnostic Biomarker and Adverse Prognostic Factor of Hepatocellular Carcinoma (HCC): Evidence from Bioinformatic Analysis.

作者信息

Wang Wensheng, Zhu Guangxi, Lai Shujie, Guo Yan, Yin Xinru, Chen Dongfeng, Wen Liangzhi

机构信息

Department of Gastroenterology, Daping Hospital, Army Medical University, Chongqing, China (mainland).

出版信息

Med Sci Monit. 2020 Feb 24;26:e919896. doi: 10.12659/MSM.919896.

Abstract

BACKGROUND Angiogenic factor with G patch and FHA domains 1 (AGGF1) is a novel identified initiator of angiogenesis through promoting the proliferation of endothelial cells. The continuous angiogenesis plays a key role in the growth, invasion, and metastasis of hepatocellular carcinoma (HCC), while the diagnostic and prognostic roles of AGGF1 for HCC need to be further studied. MATERIAL AND METHODS The mRNA sequencing datasets and clinical features of HCC patients were extracted from The Cancer Genome Atlas database. The relationship between clinical features and AGGF1 expression was analyzed by Wilcoxon test. Further validation explorations were carried out using online database Oncomine. The diagnostic receiver operating characteristic curves of AGGF1 and alpha-fetoprotein were compared to examine the diagnostic efficacy of AGGF1. Survival analysis and Gene Set Enrichment Analysis were performed to explore the prediction value and potential mechanism of AGGF1 dysregulation in HCC. RESULTS Comprehensive overexpression of AGGF1 was observed in HCC, correlating with poor overall survival. Upregulated level of AGGF1 was statistically associated with poor differentiated histological grade, advanced cancer stage and T classification. AGGF1 was a more effective diagnostic marker than alpha-fetoprotein in HCC. Several important pathways related to HCC including pathway in cancer and P53 signaling pathway were differentially enriched in the high AGGF1 expression phenotype. CONCLUSIONS AGGF1 was a potential diagnostic and prognostic marker for poor clinical outcomes in HCC patients. Moreover, vital pathways regulated by AGGF1 in HCC may include regulation of autophagy, Wnt signaling pathway, pathway in cancer, cell cycle, and P53 signaling pathway.

摘要

背景

含G结构域和FHA结构域的血管生成因子1(AGGF1)是一种新发现的通过促进内皮细胞增殖来启动血管生成的因子。持续的血管生成在肝细胞癌(HCC)的生长、侵袭和转移中起关键作用,而AGGF1对HCC的诊断和预后作用有待进一步研究。

材料与方法

从癌症基因组图谱数据库中提取HCC患者的mRNA测序数据集和临床特征。采用Wilcoxon检验分析临床特征与AGGF1表达之间的关系。使用在线数据库Oncomine进行进一步的验证探索。比较AGGF1和甲胎蛋白的诊断性受试者工作特征曲线,以检验AGGF1的诊断效能。进行生存分析和基因集富集分析,以探讨AGGF1失调在HCC中的预测价值和潜在机制。

结果

在HCC中观察到AGGF1全面过表达,与总体生存率差相关。AGGF1水平上调与组织学分级差、癌症晚期和T分期在统计学上相关。在HCC中,AGGF1是比甲胎蛋白更有效的诊断标志物。包括癌症通路和P53信号通路在内的几个与HCC相关的重要通路在高AGGF1表达表型中差异富集。

结论

AGGF1是HCC患者临床预后不良的潜在诊断和预后标志物。此外,AGGF1在HCC中调控的重要通路可能包括自噬调控、Wnt信号通路、癌症通路、细胞周期和P53信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca38/7057760/b6d942dd5d0b/medscimonit-26-e919896-g001.jpg

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