EGLN3对口腔鳞状细胞癌患者的临床预后作用

The clinical significance of EGLN3 in the patients with oral squamous cell carcinoma

目的:研究EGLN3基因对口腔鳞状细胞癌患者预后的影响意义。方法:通过二次分析口腔鳞状细胞癌基因表达数据集GSE42743,明确EGLN3基因在口腔鳞状细胞癌组织和其相应的正常口腔黏膜组织中的表达差异,探讨EGLN3(egl-9 family hypoxia inducible factor 3,egl-9家庭缺氧诱导因子3)基因与口腔鳞状细胞癌患者的年龄、性别、吸烟情况、肿瘤部位、T分期、PN分期(pathological N分期)、CN分期(clinical N分期)以及AJCC(American Joint Committee on Cancer,美国肿瘤研究联合委员会)分期、总生存期及口腔鳞状细胞癌特异性总生存期间的关系,并运用基因集富集分析方法进一步探讨EGLN3基因对口腔鳞状细胞癌细胞的具体作用机制。结果:EGLN3基因在口腔鳞状细胞癌组织中的表达显著高于癌旁正常组织(P<0.0001),高表达EGLN3的口腔鳞状细胞癌患者的T分期、CN分期(临床分期)、PN分期(病理分期)、AJCC分期方面明显劣于EGLN3低表达组口腔鳞状细胞癌患者(P=0.017,P=0.001,P=0.04,以及P=0.02),EGLN3低表达组口腔鳞状细胞癌患者的总生存期与口腔鳞状细胞癌特异性总生存期均显著优于EGLN3高表达组口腔鳞状细胞癌患者(两组P值均<0.0001)。GSEA(gene set enrichment analysis,基因集富集分析)分析提示EGLN3基因可能通过m TORC1、E2 F、MYC、NOTCH信号通路以及PI3 K-AKTm TOR、蛋白分泌、有丝分裂、细胞周期G2M检查点,糖酵解、胆固醇代谢、去折叠蛋白反应等多种生物学过程作用于口腔鳞状细胞癌细胞。结论:EGLN3基因是口腔鳞状细胞癌患者的独立预后不良因素。

Objective： To investigate the prognostic role of EGLN3 in patients with oral squamous cell carcinoma.Methods： The oral squamous cell carcinoma（ OSCC） gene expression datasets GSE42743 was reanalyzed to characterize the expression of EGLN3 gene between oral cancer patients and adjacent normal tissue,and the correlations between EGLN3 expression and the T staging,CN staging,PN staging,AJCC staging,overall survival and OSCC specific survival of oral cancer patients. Gene set enrichment analysis was applied to investigate the exact mechanisms regarding the expression of EGLN3 and the proliferation of OSCC cells. Results： The level of EGLN3 expression was significantly higher in OSCC patients than that in normal controls（ P 0. 0001）. OSCC patients with lower expression of EGLN3 were associated with better T staging,PN staging,CN staging,AJCC staging,overall survival,and OSCC specific survival compared with EGLN3 higher expression cohort. The result of GSEA indicated that EGLN3 might promote the proliferation of OSCC cells biological processes involving m TORC1,E2 F,MYC,and NOTCH signaling,protein secretion,mitotic spindle,G2 M checkpoint,glycolysis,cholesterol homeostasis and unfold protein response. Conclusion： EGLN3 might be an independent risk factor for OSCC patients.