摘要
目的分析RHEBL1基因在肺癌中的表达水平及其与临床预后的关系。方法本文通过回顾性分析肺癌基因表达数据集GSE30219和GSE19188,明确RHEBL1基因在正常肺组织和肺癌组织中的表达差异,RHEBL1基因与肺癌患者TNM分期、无进展生存期以及总生存期的关系,并运用基因集富集分析方法探讨RHEBL1基因信号富集通路。结果RHEBL1基因在肺癌组织中的表达水平为(0.182±0.449),显著高于癌旁正常肺组织的(-0.251±0.261),差异有统计学意义(P<0.01)。单因素分析显示,RHEBL1表达与T、N、M分期密切相关,而与年龄、性别无明显相关性(P>0.05)。多因素Logistic回归表明,RHEBL1表达水平与肺癌患者的年龄、T分期、N分期显著相关,差异有统计学意义(P<0.05)。生存分析显示,RHEBL1高表达组无进展生存期和总生存期明显低于RHEBL1低表达组(HR=3.045,95%CI:2.073~4.474;HR=0.320,95%CI:0.235~0.427),差异均有统计学意义(P<0.05)。多因素Cox比例风险模型分析表明,在校正年龄、性别、TNM分期等因素后,RHEBL1仍可作为肺癌患者无进展生存期(HR=1.769,95%CI:1.238~2.528)和总生存期(HR=1.856,95%CI:1.393~2.474)的独立预测因子。RHEBL1基因高表达组主要富集在MYC信号通路、DNA修复、有丝分裂、细胞周期G2M检查点、E2F信号通路、精子发生、mTORC1相关信号通路,其中以MYC相关信号通路富集最为明显。结论RHEBL1基因在体内可能促进肺癌细胞增殖,并与肺癌患者的临床预后密切相关。
Objective The aim of the present study was to analyze the clinical significance of RHEBL1 gene in the prognosis of lung cancer patients.Methods In the present study,the lung cancer gene expression datasets GSE30219 and GSE19188 were reanalyzed to determine the expression of RHEBL1 gene between lung cancer tissues and adjacent normal lung tissues and the correlations between RHEBL1 expression and the TNM staging,progression free survival and overall survival lung cancer patients were analyzed.Gene set enrichment analysis was applied to investigate the exact mechanisms regarding the expression of RHEBL1 and the proliferation of lung cancer cells.Results The level of RHEBL1 expression was significantly higher in lung cancer cells than that in normal controls[(0.182±0.449)vs.(-0.251±0.261)],P<0.01).Lung cancer patients with higher expression levels of RHEBL1 were associated with better T staging and N staging when compared with RHEBL1 low expression cohort.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis demonstrated that progression free survival(Univariate analysis:HR=3.045,95%CI:2.073~4.474;Mutivariable analysis:HR=1.769,95%CI:1.238~2.528),and overall survival(Univariate analysis:HR=0.320,95%CI:0.235~0.427;Mutivariable analysis:HR=1.856,95%CI:1.393~2.474)were higher than those of RHEBL1 low expression cohort.The result of GSEA suggested that RHEBL1 might promote the proliferation of lung cancer cells involving MYC signaling,DNA repair,mitotic spindle,G2M checkpoint,E2F signaling,spermatogenesis and mTORC1 signaling.Conclusion RHEBL1 might be an independent risk factor for lung cancer patients.
作者
熊智
XIONG Zhi(Department of Respiratory Medicine,the Second People's Hospital of Jingzhou,Jingzhou,Hubei 434000,China)
出处
《热带医学杂志》
CAS
2019年第10期1265-1270,共6页
Journal of Tropical Medicine
基金
湖北省知识创新专项(2016CFB253).
