磷酸化4E-BP1在结直肠癌中的表达及与临床病理特征、预后的关系

Expression of phosphorylated 4E-BP1 and its relationship to prognosis in colorectal cancer

目的探讨磷酸化的真核翻译起始因子结合蛋白(p-4E-BP1)在结直肠癌组织中的表达及与临床病理特征、预后的关系。方法采用免疫组化染色检测164例患者结直肠癌组织中p-4E-BP1表达,采用qRT-PCR、Western bolt法检测结直肠癌组织及其癌旁正常组织中4E-BP1、p-4E-BP1的m RNA、蛋白表达,应用Kaplan-Meier法和Cox比例风险回归模型对结直肠癌患者进行生存分析。结果 164例结直肠癌患者中p-4E-BP1均有表达,其中低表达69例(42.1%),高表达95例(57.9%)。p-4E-BP1表达与结直肠癌患者的肿瘤分化程度、浸润深度、淋巴结转移及TNM分期均有关,其中细胞分化较差、浸润较深、淋巴结转移、TNM分期较晚的结直肠癌患者p-4E-BP1表达均较高(均P<0.05)。结直肠癌组织中4E-BP1 m RNA、蛋白表达与癌旁正常组织比较,差异均无统计学意义(均P>0.05);而p-4E-BP1蛋白表达较癌旁正常组织明显增高(P<0.05)。p-4E-BP1高表达组无进展生存期、总生存期均明显短于低表达组(均P<0.05)。p-4E-BP1蛋白表达是影响患者术后总生存期、无进展生存期的独立风险因素(RR=5.414、4.754,均P<0.05)。结论 p-4E-BP1高表达与肿瘤进展以及不良预后相关,p-4E-BP1可作为临床判断结直肠癌患者预后的一个新指标。

Objective To evaluate the expression of phosphorylated eukaryotic translation initiation factor 4 E-binding protein(p-4E-BP1) and to assess its relationship with clinicopathological features and prognosis in patients with colorectal cancer. Methods The expression of p-4E-BP1 in 164 specimens of colorectal cancer tissue was detected with immunohistochemistry. The expression of 4 E-BP1 mRNA and protein in colorectal cancer and adjacent normal tissues were detected with qRT-PCR and Western bolt, respectively. Kaplan-Meier method and Cox proportional hazards regression model were used to analyze the survival of patients with colorectal cancer. Results p-4E-BP1 was positive in all colorectal cancer samples, including 95(57.9%) cases with high expression and 69(42.1%) cases with low expression. The expression level of p-4E-BP1 was significantly associated with tumor differentiation, invasive depth, lymph node metastasis and TNM stage. High expression of p-4E-BP1 was observed in colorectal cancer patients with poor differentiation, deeper infiltration, regional lymph node metastasis and later TNM stage(all P <0.05). Although there were no significant differences in mRNA and protein expression of 4 E-BP1 between tumor tissue and adjacent normal colorectal tissue, the phosphorylation level of 4 E-BP1 was markedly increased in colorectal cancer tissue(P<0.05). Kaplan-Meier survival analysis showed that the overall survival and progression-free survival of the p-4E-BP1 high expression group was significantly shorter than these of the low expression group(both P<0.05). Cox proportional hazards model revealed that p-4E-BP1 was an independent adverse prognostic factor for both overall survival(RR=5.414, P<0.05) and progression-free survival(RR=4.754, P<0.05) in colorectal cancer patients.Conclusion High p-4E-BP1 expression is associated with tumor progression and adverse prognosis. p-4E-BP1 might serve as a novel biomarker to predict the clinical outcome of patients with colorectal cancer.