结直肠癌中PHLPP2、PTEN与p-Akt1表达的相关性及其临床意义

Correlation of PHLPP2,PTEN and p-Akt1 expression in colorectal cancer and its significance

目的检测PHLPP2、PTEN与p-Akt1及其下游分子VEGF、BCL-2及Cyclin D1在结直肠癌中的表达,探讨蛋白表达的相关性及其临床意义。方法采用免疫组化En Vision法和RT-PCR法检测结直肠癌及正常结直肠黏膜组织中PHLPP2、PTEN、p-Akt1、VEGF、BCL-2及Cyclin D1的表达,并分析蛋白表达与临床病理特征及预后的相关性。结果结直肠癌组织中PHLPP2和PTEN阳性率低于正常结直肠黏膜组织;p-Akt1、VEGF、BCL-2及Cyclin D1在结直肠癌组织中的阳性率明显高于正常结直肠黏膜组织(P<0.05)。结直肠癌中PHLPP2与p-Akt1、VEGF、BCL-2、Cyclin D1表达均呈负相关(P<0.05)。PHLPP2、PTEN均阳性的结直肠癌组织中p-Akt1阳性率明显低于其他组;PHLPP2、PTEN均阴性结直肠癌组中p-Akt1阳性率明显高于其他分组(P<0.05)。PHLPP2、PTEN蛋白表达水平与分化程度及淋巴结转移具有相关性;p-Akt1蛋白表达水平与分化程度、浸润深度和淋巴结转移密切相关(P<0.05)。Kaplan-Meier分析显示,PHLPP2、PTEN、p-Akt1与结直肠癌患者预后相关。Cox回归模型分析显示,PHLPP2、PTEN、p-Akt1、分化程度及淋巴结转移是结直肠癌预后的独立危险因素。结论 PHLPP2与PTEN做为抑癌基因共同影响Akt1磷酸化,PHLPP2在结直肠癌中表达缺失与肿瘤的发生、发展及转移密切相关,可作为评估结直肠癌患者预后的潜在分子标志物。

Purpose To detect the expression of PTEN,PHLPP2,p-Akt1,VEGF,BCL-2 and Cyclin D1 in colorectal cancer,and to investigate its correlation and the clinical significance.Methods Immunohistochemistry and RT-PCR were used to detect the expression of PHLPP2,PTEN,p-Akt1,VEGF,BCL-2 and Cyclin D1.The correlation between them and the clinicopathological characteristics was analyzed.Results The positive rates of PHLPP2 and PTEN in colorectal cancer were lower than those in normal colorectal mucosa,but the expression of p-Akt1,VEGF,BCL-2 and Cyclin D1 were significantly higher in CRC(P<0.05).The expression of PHLPP2 was negatively correlated with p-Akt1,VEGF,BCL-2 and Cyclin D1 in CRC(P<0.05).The expression of p-Akt1 in PHLPP2(-)and PTEN(-)group was significantly higher than it in the other groups.The expression of p-Akt1 in PHLPP2(+)and PTEN(+)group was lower than it in the other groups.Kaplan-Meier analysis showed that 5-year survival rate was associated with PHLPP2,PTEN,p-Akt1.Multivariate analysis revealed that PHLPP2,PTEN,p-Akt1,tumor differentiation and lymph node metastasis were independent prognositic factors of colorectal cancer.The expression of PHLPP2 and PTEN were negatively correlated with differentiation and lymph node metastasis,and the expression of p-Akt1 were positively correlated with the differentiation,invasion and lymph node metastasis(P<0.05).Conclusion Tumor suppressor genes,PHLPP2 and PTEN,dephosphorylate the Akt1 together.PHLPP2 is closely related to the occurrence,development,angiogenesis and prognosis of colorectal cancer.The detection of the expression of PHLPP2 may be a potential marker for predicting the prognosis of colorectal carcinoma.