自噬相关基因LC3、Beclin-1在胰腺癌组织中的表达及意义

Expression of autophagy-related genes LC3 and Beclin-1 in pancreatic carcinoma and their clinical significance

目的探讨自噬相关基因LC3和Beclin-1在胰腺癌及正常胰腺组织中的表达及与胰腺癌发生、发展的相关性及意义。方法应用组织芯片技术和免疫组化法观察自噬相关蛋白LC3和Beclin-1在88例胰腺癌组织和11例正常胰腺组织中的表达,分析两者表达与临床病理特征及预后的关系。结果胰腺癌组织中LC3和Beclin-1蛋白高表达率(25%、52.3%)显著低于正常胰腺组织(72.7%、90.9%),差异均有统计学意义(P=0.003 7,P=0.034 4)。LC3蛋白表达与胰腺癌TNM分期及淋巴结转移相关(P=0.001,P=0.009)。Beclin-1蛋白表达与胰腺癌TNM分期相关(P=0.011)。经Spearman秩相关检验,LC3与Beclin-1蛋白在胰腺癌中的表达呈正相关(r=0.289,P=0.006 7)。Kaplan-Meier生存分析显示,LC3或Beclin-1蛋白高表达患者生存时间相对缩短(P=0.001 8,P<0.001)。Cox风险模型分析显示,临床TNM分期、淋巴结转移及LC3和Beclin-1蛋白表达与患者生存时间有关(P均<0.05),其中临床TNM分期和Beclin-1蛋白表达是影响患者生存期的独立预后因素(P<0.001,P=0.012)。结论自噬相关基因LC3和Beclin-1在胰腺癌发生、发展中可能起重要作用,对LC3和Beclin-1蛋白表达的联合检测有助于胰腺癌的预后判断。

Purpose To investigate the expression of autophagy-related genes LC3 and Beclin-1 in pancreatic carcinoma,and to explore their correlations to the tumorigenesis and development of pancreatic carcinoma.Methods Tissue microarrays and immunohistochemistry were used to detect the expression of autophagy-related proteins LC3 and Beclin-1 in 88 specimens of pancreatic carcinoma and 11 specimens of normal pancreas.The correlations of LC3 and Beclin-1 expression to the clinicopathological parameters were also analyzed.Results The high-expression rates of LC3 and Beclin-1 were significantly lower in pancreatic carcinoma than those in normal pancreas(P=0.003 7,P=0.034 4).The expression of LC3 was associated with clinical TNM stages and metastasis of lymph nodes(P=0.001,P=0.009).The expression of Beclin-1 was related to clinical TNM stages(P=0.011).LC3 expression was found to have positive correlation with Beclin-1 expression in pancreatic carcinoma by the Spearman rank test(r=0.289,P=0.006 7).The survival analysis showed that the survival time of patients with high-expression of LC3 or Beclin-1 was significantly shorter(P=0.001 8,P<0.001).The Cox risk analysis revealed that the survival time of patients with pancreatic carcinoma was correlated with clinical TNM stages,metastasis of lymph nodes,LC3 expression and Beclin-1 expression(P<0.05),and what’s more,clinical TNM stages and Beclin-1 expression were two independent prognostic indexes for pancreatic carcinoma(P<0.001,P=0.012).Conclusion The autophagy-related genes LC3 and Beclin-1 may play an important role in tumorigenesis and development of pancreatic carcinoma.The combined examination of LC3 and Beclin-1 protein may be helpful for the prognosis judgment of pancreatic carcinoma.