Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma

doi:10.3389/fonc.2021.789244

	Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma
	Guo, Zhenying 1,2,3,7,8; Shen, Li 4; Li, Ningning 1,2; Wu, Xiaoxiao 1,2; Wang, Canming 1,2; Gu, Zheng 5; Chen, Zhongjian 2,6; Liu, Junping 2,6; Mao, Weimin 2,3,6; Han, Yuchen 7,8
刊名	FRONTIERS IN ONCOLOGY
	2021-12-08
卷号	11
关键词	malignant mesothelioma bioinformatics biomarkers tissue microarray Aurora kinase A
ISSN号	2234-943X
DOI	10.3389/fonc.2021.789244
通讯作者	Han, Yuchen(ychan@cmu.edu.cn)
英文摘要	BackgroundMalignant mesothelioma (MM) is a highly aggressive cancer with a poor prognosis. Despite the use of several well-known markers, the diagnosis of MM is still challenging in some cases. we applied bioinformatics to identify key genes and screen for diagnostic and prognostic markers of MM. MethodsThe expression profiles of GSE2549 and GSE112154 microarray datasets from the Gene Expression Omnibus database contained 87 cases of MM tissue and 8 cases of normal mesothelial tissue in total. The GEO2R tool was used to detect differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using DAVID Bioinformatics Resources. The DEGs protein-protein interaction networks were constructed from the STRING database. Cytoscape was used to identify significant modules and hub genes. The GEPIA database was used to explore relationships between hub genes and prognosis of MM. Immunohistochemistry was used to analyze protein expression in tissue microarrays with 47 Chinese MM tissues. Statistical analyses diagnostic and prognostic values. Results346 DEGs were identified: 111 genes upregulated, and 235 downregulated. GO analysis showed that the primary biological processes of these DEGs were cell adhesion, leukocyte migration, and angiogenesis. The main cellular components included the extracellular space, extracellular exosome, and extracellular region. The molecular functions were integrin binding, heparin binding, and calcium ion binding. KEGG pathway analysis showed that DEGs are primarily involved in PPAR signaling pathway, extracellular matrix-receptor interactions, and regulation of lipolysis in adipocytes. Survival analysis showed that seven genes-AURKA, GAPDH, TOP2A, PPARG, SCD, FABP4, and CEBPA-may be potential prognostic markers for MM. Immunohistochemical studies showed that Aurora kinase A (AURKA gene encode, Aurora-A) and GAPDH were highly expressed in MM tissue in comparison with normal mesothelial tissue. Kaplan-Meier analysis confirmed a correlation between Aurora-A protein expression and overall survival but did not confirm a correlation with GAPDH. The receiver operating characteristic curves of Aurora-A protein expression suggested acceptable accuracy (AUC = 0.827; 95% CI [0.6686 to 0.9535]; p = 0.04). The sensitivity and specificity of Aurora-A were 83.33% and 77.78%, respectively. ConclusionAurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for MM.
资助项目	National Natural Science Foundation of China[.81672315] ; National Natural Science Foundation of China[81672315] ; Natural Science Foundation of Zhejiang Province of China[LY21H160002] ; Medical and Health Science and Technology Project of Zhejiang Province[2021KY543] ; Key R&D Program Projects in Zhejiang Province[2018C04009] ; Clinical Research Fund of Zhejiang Medical Association[2019ZYC-A77] ; International Cooperation Project of Zhejiang Basic Public Technology Research Program[LGJ20H010001] ; Projects of Zhejiang Province Medical and Health Science and Technology Plan[2017KY256] ; Medical and Health Science and Technology Project of Zhejiang Province[2021KY543] ; Medical and Health Science and Technology Plan Project of Zhejiang Province[2019PY033] ; Research Program of Department of Science and Technology of Zhejiang Province[LGF19H180019] ; Research Program of Zhejiang University 2018 Zhejiang Provincial Department of Education General Research Project (Natural Science)[Y201840845] ; [82072577] ; [2020RC047]
WOS关键词	INVESTIGATIONAL AURORA ; CANCER-CELLS ; PHASE-II ; INHIBITOR ; ALISERTIB ; INDUCTION ; APOPTOSIS
WOS研究方向	Oncology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000732819300001
资助机构	National Natural Science Foundation of China ; Natural Science Foundation of Zhejiang Province of China ; Medical and Health Science and Technology Project of Zhejiang Province ; Key R&D Program Projects in Zhejiang Province ; Clinical Research Fund of Zhejiang Medical Association ; International Cooperation Project of Zhejiang Basic Public Technology Research Program ; Projects of Zhejiang Province Medical and Health Science and Technology Plan ; Medical and Health Science and Technology Project of Zhejiang Province ; Medical and Health Science and Technology Plan Project of Zhejiang Province ; Research Program of Department of Science and Technology of Zhejiang Province ; Research Program of Zhejiang University 2018 Zhejiang Provincial Department of Education General Research Project (Natural Science)
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/126920]
专题	中国科学院合肥物质科学研究院
通讯作者	Han, Yuchen
作者单位	1.Univ Chinese Acad Sci, Canc Hosp, Dept Pathol, Zhejiang Canc Hosp, Hangzhou, Peoples R China 2.Chinese Acad Sci, Inst Basic Med & Canc, Hangzhou, Peoples R China 3.Zhejiang Canc Hosp, Zhejiang Key Lab Diag & Treatment Technol Thorac, Hangzhou, Peoples R China 4.Zhejiang Univ, Sir Run Run Shaw Hosp, Off Educ, Sch Med, Hangzhou, Peoples R China 5.Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Clin Med Engn, Hangzhou, Peoples R China 6.Univ Chinese Acad Sci, Canc Hosp, Zhejiang Canc Hosp, Hangzhou, Peoples R China 7.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Pathol, Shanghai, Peoples R China 8.Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Guo, Zhenying,Shen, Li,Li, Ningning,et al. Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma[J]. FRONTIERS IN ONCOLOGY,2021,11.
APA	Guo, Zhenying.,Shen, Li.,Li, Ningning.,Wu, Xiaoxiao.,Wang, Canming.,...&Han, Yuchen.(2021).Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma.FRONTIERS IN ONCOLOGY,11.
MLA	Guo, Zhenying,et al."Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma".FRONTIERS IN ONCOLOGY 11(2021).