胰腺癌中OPG表达及与预后的相关性

Expression of OPG in pancreatic ductal adenocarcinoma and its correlation with prognosis

目的探讨胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)中骨保护素(osteoprotegerin,OPG)的表达与临床病理学特征、KRAS基因突变及预后的相关性。方法收集2008~2012年南京医科大学第一附属医院PDAC标本102例,制作组织芯片,采用免疫组化法检测OPG在PDAC中的表达。采用荧光定量PCR法检测其中46例肿瘤组织KRAS基因第12、13号外显子突变情况。结果肿瘤组织中OPG与癌旁组织相比,其表达更高。46例KRAS基因突变检测中有24例野生型(52.2%),22例突变型(47.8%)。相关性分析显示KRAS基因突变与糖尿病有关(P=0.025),与OPG表达及其他临床病理特征无相关性(P>0.05)。Cox单因素生存分析显示组织大小(P=0.008)、分化程度(P<0.001)、肠系膜上动脉受侵犯(P=0.043)、肠系膜上静脉受侵犯(P=0.004)、门静脉受侵犯(P=0.033)、术后化疗(P=0.023)、OPG表达(P<0.001)与PDAC预后显著相关。Cox多因素生存分析显示OPG高表达(P<0.001)是PDAC患者总生存期的独立预后因素。结论OPG高表达提示PDAC患者预后差,其可以作为PDAC预后的生物学标志物。

Purpose To investigate the expression of osteoprotegerin(OPG)in pancreatic ductal adenocarcinoma and its correlation with the clinicopathological features,KRAS mutation and prognosis.Methods A total of 102 cases of pancreatic ductal adenocarcinoma were collected from the First Affiliated Hospital of Nanjing Medical University from 2008 to 2012.Tissue microarray was used to detect the expression of OPG in the tumor cells by immunohistochemistry.The mutations of exons 12 and 13 of KRAS gene were detected in 46 patients by RT-PCR.Results OPG showed higher expression in cancer tissues.Of the 46 cases of KRAS mutation analyzed,24 were wild-type(52.2%)and 22 had mutations(47.8%).Correlation analysis showed that tumor KRAS mutation was only associated with diabetes(P=0.025),and there was no correlation with OPG expression and other clinical data(P>0.05).Univariate survival analysis showed that the tumor size,grading,invasion of superior mesenteric artery,superior mesenteric vein and portal vein,postoperative chemotherapy,OPG expression were significantly correlated with the prognosis of pancreatic ductal adenocarcinoma(P<0.05).Multivariate analysis of survival showed the high expression of OPG in tumor cells was an independent risk factor for overall survival(P<0.001).Conclusion Higher OPG expression suggests poorer prognosis in pancreatic ductal adenocarcinoma.OPG may be a novel prognostic biomarker in pancreatic ductal adenocarcinoma.