MACC1与c-Met基因在胰腺癌组织中的表达及预后意义

Expression and Prognostic Significance of MACC1 and c-Met Genes in Pancreatic Cancer

目的探究MACC1与c-Met基因在胰腺癌组织中的表达及预后意义。方法应用免疫组化法检测各标本中MACCI和c-Met蛋白的表达情况,统计学分析MACC1和c-Met表达水平与临床病理特征的关系;分别检测MACC1和c-Met在各细胞系中的表达情况,并选取高表达MACC1与c-Met的两组细胞株,通过RNA干扰技术抑制MACC1表达,48H后采用RT-PCR技术检测MACC1与c-Met;分别采用流式细胞仪、划痕实验及Transwell实验检测干扰后两组细胞的细胞增殖、凋亡、迁移及侵袭能力的变化;采用免疫印迹法检测干扰后两组细胞的MACC1与c-Met蛋白变化,并进一步研究相关信号通路的变化。结果MACC1和c-Met蛋白在胰腺癌组织中的高表达率明显增加(P<0.05),且随着肿瘤分期的增高及淋巴结的转移,其表达量均有所增加(P<0.05)。在RNA干扰后,MACCI和c-Met蛋白表达水平较对照组均明显降低(P<0.05);且细胞增殖、细胞迁移和侵袭能力均明显降低,细胞凋亡率明显增多。此外,下调MACC1表达抑制了Notch1、Hey1、Hes1等Notch信号通路相关蛋白的表达,同时,p53、MDM2等p53信号通路相关蛋白表达也明显改变。结论在胰腺癌中,MACC1和c-Met高表达与肿瘤分期及淋巴结转移密切相关。下调MACC1可以抑制凋亡蛋白的表达、胰腺癌细胞的增殖、迁移和侵袭,促进癌细胞凋亡,还可抑制Ras/ERK、Notch以及p53信号通路。MACC1和c-Met与胰腺癌的发生发展密切相关,可作为判断胰腺癌患者预后的重要指标。

Objective To explore the expression and prognostic significance of MACC1 and c-Met genes in pancreatic cancer.Methods Immunohistochemical method was used to detect the expression of MACCI and c-Met protein in each specimen,and the relationship between the expression level of MACC1 and c-Met and clinicopathological features was statistically analyzed.The expression of MACC1 and c-Met in each cell line was detected respectively,and two groups of cell lines with high expression of MACC1 and c-Met were selected,and the expression of MACC1 was inhibited by RNA interference technology.After 48H,the expression of MACC1 and c-met was detected by RT-PCR technology.Flow cytometry,scratch test and Transwell test were used to detect the changes of cell proliferation,apoptosis,migration and invasion ability of the two groups after interference.The changes of MACC1 and c-Met protein in the two groups were detected by western blot,and the changes of related signal pathways were further studied.Results The high expression rate of MACC1 and c-Met protein in pancreatic cancer tissues increased significantly(P<0.05),and their expression levels increased with the increase of tumor stage and lymph node metastasis(P<0.05).After RNA interference,the expression levels of MACCI and c-Met protein were significantly lower than those of the control group(P<0.05).Moreover,cell proliferation,cell migration and invasion ability were significantly reduced,and cell apoptosis rate was significantly increased.In addition,down-regulation of MACC1 expression inhibited the expression of Notch1,Hey1,Hes1 and other Notch signaling pathway related proteins,and at the same time,the expression of p53 signaling pathway related proteins such as p53 and MDM2 also changed significantly.Conclusion In pancreatic cancer,the high expression of MACC1 and c-Met is closely related to tumor stage and lymph node metastasis.Down-regulation of MACC1 can inhibit the expression of apoptotic protein,the proliferation,migration and invasion of pancreatic cancer cells,promote the apoptosis of cancer cells,and also inhibit Ras/ERK,Notch and p53 signaling pathways.MACC1 and c-Met are closely related to the occurrence and development of pancreatic cancer,and can be used as important indicators to judge the prognosis of patients with pancreatic cancer.