肝细胞核因子4α在直肠癌中的临床意义及其与预后的关系

Clinical significance of hepatocyte nuclear factor 4αin rectal cancer and its relationship with prognosis

目的：探讨肝细胞核因子4α（HNF4α）在直肠癌中的临床意义及其与预后的关系。方法应用实时PCR法检测HNF4α在直肠癌中mRNA的表达水平，采用免疫组织化学法检测HNF4α蛋白表达水平，结合临床资料分析HNF4α与临床病理特征之间的关系，运用Kaplan-Meier法进行单因素生存分析，应用Cox回归模型进行多因素生存分析。结果在直肠癌组织中，HNF4α的mRNA（t＝6．092， P＜0．001）和蛋白（χ2＝15．230，P＜0．001）表达水平均低于癌旁组织，其蛋白表达与肿瘤临床分期（χ2＝48．311，P＜0．001）、浸润深度（χ2＝23．911，P＜0．001）、分化程度（χ2＝20．787，P＜0．001）、淋巴结转移（χ2＝39．064，P＜0．001）以及远处转移（χ2＝5．146，P＝0．04）相关，与性别和年龄无关。HNF4α低表达组患者术后3年生存率（43．8％）低于高表达组（95．5％），差异具有统计学意义（P＜0．001）。单因素生存分析表明，患者的预后与HNF4α表达（χ2＝28．778，P＜0．001）、分化程度（χ2＝26．680，P＜0．001）、临床分期（χ2＝32．702，P＜0．001）、肿瘤浸润深度（χ2＝6．226，P＝0．013）、淋巴结转移（χ2＝15．270，P＜0．001）以及远处转移（χ2＝21．817，P＜0．001）相关，而与性别及年龄无关。多因素生存分析表明， HNF4α低表达（RR＝6．084，P＝0．028）是直肠癌患者预后评价的独立因素。结论 HNF4α参与直肠癌的发生、进展，是判断其预后的独立因子，可能成为直肠癌治疗的有效靶点。

Objective To investigate the clinical significance of hepatocyte nuclear factor 4α（HNF4α）in rectal cancer and its relationship with prognosis.Methods Real-time PCR was designed to detect the expression of HNF4αon mRNA level and the immunohistochemistry was used to determine the expression of HNF4αon protein level in rectal cancer tissue.The relationship between HNF4αexpression and clinical characteristics was also analysed.The Kaplan-Meier method was used for univariate analysis and a Cox proportional hazards regression model was performed for multivariate analysis.Results HNF4αwas low expressed both on mRNA （t=6.092,P＆lt;0.001）and protein level （χ2 =15.230,P＆lt;0.001）in rectal cancer tissue.HNF4αexpression on protein level was related with the clinical stage （χ2 =48.311,P＆lt;0.001）,depth of invasion （χ2 =23.911,P＆lt;0.001）,histological differentiation （χ2 =20.787,P＆lt;0.001）,lymph node metastasis （χ2 =39.064,P＆lt;0.001）and distant metastasis （χ2 =5.146,P=0.04）,while age and gender were not relevant.The cumulative 3-year overall survival of patients with low HNF4αexpression （43.8%）was much worse than the patients with high HNF4αexpression （95 .5%）,and the difference was statistically sig-nificant （P＆lt;0.001）.Univariate analysis revealed that HNF4αexpression （χ2 =28.778,P＆lt;0.001）,differ-entiation （χ2 =26.680,P＆lt;0.001 ）,clinical stage （χ2 =32.702,P＆lt;0.001 ）,depth of invasion （χ2 =6.226,P=0.013）,lymph node invasion （χ2 =15.270,P＆lt;0.001）and distant metastasis （χ2 =21.817, P＆lt;0.001）were statistically significant worse predictors for rectal cancer,whereas age and gender were not rel-evant.The multivariate Cox proportional hazard analysis revealed that HNF4αlow expression （RR=6.084, P=0.028）was independent prognostic markers for 3-year overall survival in the patients with rectal cancer. Conclusion HNF4αwas closely related to the tumorigenesis and progression of rectal cancer,which is an independent prognostic marker for rectal cancer,and which may be an effective target for the therapy of rectal cancer.