E2F8在人结直肠癌中的表达及其与患者预后的关系

Expression of E2F8 in human colorectal cancer and its relationship with the prognosis of patients

目的探讨腺病毒E2启动子结合因子8(E2F8)在结直肠癌(CRC)中的表达及其对结直肠癌患者预后的影响。方法分析癌症基因组图谱(TCGA)数据库和基因组织表达(GTEx)数据库中E2F8在结直肠癌中的mRNA表达水平。通过实时荧光定量PCR方法(qPCR)和蛋白质免疫印迹(Western blot)方法分别检测E2F8在结直肠癌组织和细胞中的表达量。98例结直肠癌患者肿瘤及癌旁组织经免疫组化染色方法分析E2F8蛋白表达与患者临床特征和预后的关系,采用COX比例风险模型分析CRC预后的影响因素。结果TCGA数据库及临床样本中E2F8在肿瘤组织中的表达水平均高于正常组织。结直肠癌细胞系中E2F8表达水平除HCT116、HCT15以外均较正常结肠上皮细胞系高。高表达E2F8的患者总生存期、无疾病生存期、无转移生存期均短于低表达E2F8的患者(均P<0.01),高表达E2F8的结直肠癌组织Dukes分期较晚(P<0.05)。单因素COX回归模型分析发现,女性(HR=2.009,95%CI:1.139~3.544)、淋巴结侵犯(HR=1.780,95%CI:1.005~3.150)、Dukes C/D期(HR=2.538,95%CI:1.393~4.623)、TNM III/IV期(HR=2.894,95%CI:1.554~5.392)、E2F8高表达(HR=2.807,95%CI:1.540~5.118)与结直肠癌患者不良预后相关(均P<0.05)。多因素COX回归模型分析发现,E2F8高表达(HR=2.747,95%CI:1.447~5.216)和较晚的TNM分期(HR=5.543,95%CI:1.537~19.990)是结直肠肿瘤患者不良预后的独立危险因素(均P<0.05)。结论E2F8在结直肠癌中较高表达,结直肠癌组织中高表达E2F8与结直肠癌患者Dukes分期晚和不良预后有关,E2F8高表达是结直肠肿瘤患者不良预后的独立危险因素,E2F8可作为结直肠癌患者疾病进展及预后的潜在标志物。

Objective To investigate the expression of adenovirus E2 promoter binding factor 8(E2F8)in colorectal cancer(CRC)and its effect on the prognosis of colorectal cancer patients.Methods The mRNA expression levels of E2F8 in colorectal cancer were analyzed in Cancer Genome Atlas(TCGA)database and Gene Tissue Expression(GTEx)database.The expression of E2F8 in colorectal cancer tissues and cells was detected by real-time fluorescence quantitative PCR(qPCR)and Western blot.Immunohistochemical staining was used to analyze the relationship between E2F8 protein expression and clinical features and prognosis of 98 patients with colorectal cancer.COX proportional risk model was used to analyze the prognostic factors of CRC.Results The expression level of E2F8 in tumor tissues was higher than that in normal tissues in TCGA database and clinical samples.E2F8 expression levels in colorectal cancer cell lines were higher than normal colon epithelial cell lines except HCT116 and HCT15.The overall survival,disease-free survival and metastasis-free survival of patients with high expression of E2F8 were shorter than those with low expression of E2F8(all P<0.01),and the Dukes stage of colorectal cancer tissues with high expression of E2F8 was later(P<0.05).Univariate COX regression model analysis showed that women(HR=2.009,95%CI:1.139-3.544),lymph node invasion(HR=1.780,95%CI:1.005-3.150),Dukes C/D stage(HR=2.538,95%CI:1.393-4.623),TNM III/IV(HR=2.894,95%CI:1.554-5.392),and high expression of E2F8(HR=2.807,95%CI:1.540-5.118)were associated with poor prognosis in colorectal cancer patients(all P<0.05).Multivariate COX regression model analysis showed that high expression of E2F8(HR=2.747,95%CI:1.447-5.216)and late TNM stage(HR=5.543,95%CI:1.537-19.990)were independent risk factors for poor prognosis in patients with colorectal tumors(all P<0.05).Conclusion E2F8 is highly expressed in colorectal cancer,and high expression of E2F8 in colorectal cancer tissues is associated with late Dukes staging and poor prognosis in colorectal cancer patients.High expression of E2F8 is an independent risk factor for poor prognosis in colorectal cancer patients,and E2F8 can be used as a potential marker for disease progression and prognosis in colorectal cancer patients.