胰腺癌患者沉默信息调节因子1表达水平及其临床意义

Expression level and clinical significance of SIRT1 in patients with pancreatic cancer

目的检测胰腺癌患者癌组织中沉默信息调节因子1(SIRT1)mRNA及蛋白表达水平,探讨其与胰腺癌临床病理之间的关系,评价其对胰腺癌辅助诊断及判断预后的临床意义。方法选择2010年2月—2012年6月右江民族医学院附属医院胰腺癌患者手术切除标本46例,用免疫分析方法检测癌组织中SIRT1蛋白表达,并以25例急慢性胰腺炎患者手术切除胰腺组织标本作为对照。同时取其中31例新鲜胰腺癌组织,以21例新鲜胰腺炎组织作为对照,用实时荧光定量PCR方法检测SIRT1 mRNA在患者中的表达情况。分析SIRT1表达与胰腺癌患者预后的关系。结果新鲜癌组织中SIRTl mRNA及其蛋白表达阳性率均较新鲜胰腺炎组织增高(3.54±0.63 vs.1.42±0.47,t=13.128,P<0.05);胰腺炎组织蜡块SIRT1蛋白的阳性率为44.0%(11/25),低于胰腺癌组织蜡块的84.8%(39/46),差异有统计学意义(x^2=12.934,P<0.05)。在胰腺癌组织中,SIRT1蛋白表达在不同肿瘤分期、肿瘤大小、有无淋巴结转移及CA199水平间均存在显著差异(P<0.05),且SIRTl阴性患者的生存曲线优于SIRT1阳性患者,差异有统计学意义(P<0.05)。Cox回归模型分析表明,肿瘤大小、临床TNM分期是胰腺癌患者3~5年无瘤生存率和总生存率的独立预后因素(P均<0.05)。结论 SIRT1基凶在胰腺癌组织中高表达,SIRT1蛋白的表达在不同肿瘤分期、肿瘤大小、有无淋巴结转移、CA199水平分组中存在显著差异;SIRT1的高表达是胰腺癌患者预后不良因素,其表达水平对胰腺癌的辅助诊断及预后判断具有一定的意义。

Objective To detect silent information regulatorl（SIRT1） mRNA and protein expression levels of pancreatic cancer tissues,investigate its relativity with the clinicopathology in pancreatic cancer and evaluate its clinical significance in the auxiliary diagnosis and prognosis of pancreatic cancer.Methods From Febrary 2010 to June 2012,SIRTl mRNA expression was detected by real-time PCR in 31 fresh pancreas cancer tissues,which were collected in Affiliated Hospital of YouJiang Medical College,meanwhile 21 pancreatitis tissues were paired as control.And SIRTl protein expression level was also measured by immunochemistry in 46 cases of pancreas cancer tissues and 25 paired cases of acute or chronic pancreatitis tissues.The relationship between SIRTl expression and prognosis of pancreatic cancer were analyzed.Combined with clinicopathological data and follow-up data,statistical analysis was performed by using SPSS 19.0 statistical software.Results The positive rates of expression levels of SIRTl mRNA and protein in the patients with pancreas cancer was significant higher than that in the pancreatitis controls（P〈0.05）.The positive rate of pancreatitis paraffin block of SIRTl protein was 44.0%（11/25）,which was lower than pancreatic cancer paraffin block of 84.8%（39/46）,the differences was statistically significant（x^2 = 12.934,P〈0.05）.In pancreatic cancer tissues,SIRTl protein expressions in different tumor stage,tumor size,lymph node metastasis and CA199 levels all exist difference.The survival curve of SIRTl negative patients was better than that of SIRTl positive patients;the difference was statistically significant（P〈0.05）.Cox regression model analysis showed that the tumor size and clinical TNM staging were independent prognostic factors for 3-5 years in pancreas cancer.Conclusion The SIRT1 gene and protein is highly expressed in the pancreas cancer,and there are strong correlations to pathological stage,tumor size,lymphoid metastasis and CA199 level.SIRT1 expression is a prognostic factor in patients with pancreatic cancer,and its expression level has certain significance for the diagnosis and prognosis of pancreas cancer.