miR-21调控胰腺癌潜在靶基因的分子机制及临床意义

Molecular mechanism of miR-21 regulating potential target gene of pancreatic cancer and its clinical significance

目的:明确miR-21是调控胰腺导管腺癌潜在基因(PTEN、Bcl-2、c-Myc)的重要靶点及分析miR-21在胰腺导管腺癌组织中的表达情况及临床意义。方法:通过Real-time PCR及免疫组化的方法检测miR-21、PTEN、Bcl-2和c-Myc在胰腺导管腺癌组织和癌旁胰腺组织中的表达情况;用χ^(2)检验分析在胰腺导管腺癌组织中miR-21表达与PTEN、Bcl-2和c-Myc表达之间的相关性及miR-21表达与胰腺癌患者临床病理特征的关系;用Kaplan-Meier单因素分析计算累积生存率和Log-rank检验分析胰腺癌组织中miR-21表达与胰腺癌患者术后预后的关系。结果:胰腺导管腺癌组织中miR-21、Bcl-2、c-Myc表达水平明显升高,分别与对照组相比差异均具有统计学意义(P<0.05)。胰腺导管腺癌组织中PTEN表达较对照组明显降低,差异具有统计学意义(P<0.05)。胰腺导管腺癌组织中miR-21表达与PTEN表达呈负相关,miR-21表达与c-Myc、Bcl-2表达呈正相关,差异均具有统计学意义(P<0.05)。miR-21表达与患者的性别、年龄、肿瘤分化程度、CA19-9水平、肿瘤位置无关(P>0.05),而与肿瘤的大小、TNM分期和淋巴结转移相关(P<0.05)。miR-21高表达组患者的生存率明显低于miR-21低表达组患者(P<0.05)。结论:在胰腺导管腺癌中miR-21可作为调控PTEN、Bcl-2和c-Myc的关键靶点;miR-21在胰腺癌组织中明显高表达且与患者临床病理特征密切相关,可作为早期诊断及预后的有效指标。

Objective:To confirm that miR-21 is an important target for regulating potential genes(PTEN,Bcl-2,c-Myc)of pancreatic ductal adenocarcinoma,and to analyze the expression and clinical significance of miR-21 in pancreatic ductal adenocarcinoma.Methods:The expression of miR-21,PTEN,Bcl-2 and c-Myc in pancreatic ductal adenocarcinoma and paracancerous pancreatic tissues was detected by Real-time PCR and immunohistochemistry.χ^(2)test was used to analyze the correlation between the expression of miR-21 and the expression levels of PTEN,Bcl-2 and c-Myc in pancreatic ductal adenocarcinoma and the correlation between the expression of miR-21 and the clinicopathological features of pancreatic cancer patients.Kaplan-Meier single factor analysis was used to calculate the cumulative survival rate and Log-rank test was used to analyze the relationship between the expression of miR-21 in pancreatic cancer tissue and the postoperative prognosis of pancreatic cancer patients.Results:The expression levels of miR-21,Bcl-2 and c-Myc in pancreatic ductal adenocarcinoma were significantly higher than those in the control group(P<0.05).PTEN expression in pancreatic ductal adenocarcinoma was significantly lower than that in the control group(P<0.05).There was a negative correlation between the expression of miR-21 and PTEN in pancreatic ductal adenocarcinoma,and a positive correlation between the expression of miR-21 and the expression of c-Myc and Bcl-2 in pancreatic ductal adenocarcinoma(P<0.05).miR-21 expression was not related to gender,age,tumor differentiation,CA19-9 level and tumor location(P>0.05),but related to tumor size,TNM stage and lymph node metastasis(P<0.05).The survival rate of patients with high expression of miR-21 was significantly lower than that of patients with low expression of miR-21(P<0.05).Conclusion:miR-21 may be a key target in the regulation of PTEN,Bcl-2 and c-Myc in pancreatic ductal adenocarcinoma.miR-21 is highly expressed in pancreatic cancer tissue and is closely related to clinicopathological features,which can be used as an effective indicator for early diagnosis and prognosis.