Wnt5a在胰腺癌及癌前病变中的表达差异分析

Different expressions of Wnt5a in pancreatic cancer and precancerous lesions

目的检测Wnt5a基因在不同胰腺组织中的蛋白表达水平,探讨其在胰腺导管腺癌(pancreatic ductal adenocar-cinoma,PDAC)发生中的作用,为胰腺癌的早期诊疗提供新线索。方法免疫组化SP法检测Wnt5a在21灶正常胰腺导管(normal pancreatic duct,NP)、73灶胰腺上皮内瘤变(pancreatic intraepithelial neoplasia,PanIN)-1、29灶PanIN-2、16灶PanIN-3、20例胰腺导管内乳头状黏液性肿瘤(intraductal papillary mucinous neoplasm,IPMN)腺瘤(IPMN-adenoma,IPMA)、13例IPMN交界瘤(IPMN-borderline,IPMB)、19例IPMN黏液癌(IPMN-carcinoma,IPMC)及50例PDAC组织中的蛋白表达。分析Wnt5a的表达与PDAC患者临床病理特征及患者术后生存期的关系。结果随着组织病变级别升高,Wnt5a表达逐渐增强,各组Wnt5a的免疫组化评分分别为NP(0)、PanIN-1(1.90±1.192)、PanIN-2(3.03±1.322)、PanIN-3(4.88±1.455)、IPMA(1.40±0.940)、IPMB(2.62±1.502)、IPMC(3.00±1.374)、PDAC(3.11±2.635)。Wnt5a的表达与肿瘤的增殖活度、远处转移、TNM分期及患者术后生存期相关(P<0.05),Wnt5a高表达组、低表达组的中位生存期分别为15个月和21个月(P=0.015)。结论 Wnt5a参与了PDAC的发生、发展;Wnt5a表达增强是PDAC的早期事件;Wnt5a的持续表达和过度表达影响了胰腺癌的增殖、侵袭和转移过程,并预示患者预后不良。

Objective To observe the expression of Wnt5a protein in different pancreatic tissues and to evaluate the role of Wnt5a in the carcinogenesis of pancreatic ductal adenocarcinoma（PDAC）,so as to provide new clues for the diagnosis and treatment of pancreatic cancer.Methods Immunohistochemical SP method was used to examine the expressions of Wnt5a protein in 21 normal pancreatic duct tissues,73 pancreatic intraepithelial neoplasia（PanIN）-1 tissues,29 PanIN-2,16 PanIN-3 tissues,20 intraductal papillary mucinous neoplasm（IPMN） adenoma（IPMA） tissues,13 IPMN-borderline（IPMB） tissues,19 IPMN-carcinoma（IPMC） tissues and 50 PDAC tissues.The correlation of Wnt5a expression with clinicopathologic characteristics and postoperative survival of PDAC patients was analyzed.Results Wnt5a expression increased with the progression of the lesions in the following order： NP（0）→PanIN-1（1.90±1.192）→PanIN-2（3.03±1.322）→PanIN-3（4.88±1.455） or NP（0）→IPMA（1.40±0.940）→IPMB（2.62±1.502）→IPMC（3.00±1.374）,and PDAC（3.11±2.635）.Wnt5a expression was significantly correlated with tumor proliferation activity,distant metastasis,TNM staging and postoperative survival（P0.05）.The median survival periods of PDAC patients with high and low Wnt5 expression were 15 months and 21 months,respectively（P=0.015）.Conclusion Wnt5a is involved in the development and progression of PDAC.Enhancement of Wnt5a expression is an early event in PDAC;sustained or over-expression of Wnt5a may affect the proliferation,invasion and metastases of pancreatic cancer cells,and may indicate a poor prognosis.