胰腺导管腺癌中酪氨酸蛋白激酶-7的表达及临床意义

The expression of PTK7 in pancreatic ductal adenocarcinoma and its clinical significance

目的:探讨酪氨酸蛋白激酶-7(protein tyrosine kinase-7,PTK7)在胰腺导管腺癌组织中的表达及其临床意义。方法:回顾性分析天津医科大学肿瘤医院2011年5月至2016年1月接受胰腺癌根治手术治疗的85例胰腺癌患者的临床与随访资料。采用免疫组织化学法检测85例胰腺癌组织和对应的癌旁组织中PTK7的表达,分析其与临床病理学特征及预后的关系。结果:PTK7的阳性表达主要在细胞质内,呈棕黄色颗粒。PTK7在胰腺癌和癌旁组织中的阳性表达率分别为70.6%(60/85)和52.9%(45/85),前者表达率显著高于后者,差异具有统计学意义(P<0.05)。PTK7的异常表达与肿瘤分期、淋巴结转移和脉管内瘤栓相关(P<0.05)。生存分析提示在胰腺导管腺癌中PTK7高表达的患者生存时间和肿瘤无进展时间明显短于低表达的患者(均P<0.05)。shRNA成功干扰PTK7建立细胞稳系后,MTT和克隆形成结果显示,shRNA实验组较对照组细胞存活数显著减少(P<0.05),克隆形成数显著减少(P<0.05),增殖相关蛋白Ki67和PCNA的表达水平显著降低(均P<0.05)。结论:胰腺导管腺癌组织中PTK7表达水平上调,且与胰腺癌肿瘤分期、淋巴结转移、脉管内瘤栓有关,其表达可能提示预后不良。在胰腺癌细胞系中,PTK7能通过调节增殖相关因子Ki-67和PCNA的水平而促进胰腺癌细胞的增殖。

Objective:To explore the expression of PTK7 in pancreatic ductal adenocarcinoma and its clinical significance.Methods:The clinical and follow-up data of 85 patients with pancreatic ductal adenocarcinoma who underwent radical surgery at TianjinMedical University Cancer Institute and Hospital from May 2011 to January 2016 were analyzed.The expression of PTK7 in 85 pancreatic cancer tissues and the corresponding para-cancer tissues was detected by immunohistochemistry,and the relationship between PTK7 expression level and the clinical pathological features and prognosis was analyzed.Results:Positive expression of PTK7 was observed mainly in the cytoplasm,presenting as brownish yellow granules.It was noted that expression of PTK7 in pancreatic ductal adenocarcinoma tissues and para-carcinoma tissues was 70.6%(60/85)and 52.9%(45/85),respectively,and the positive rate in pancreatic ductal adenocarcinoma tissues was significantly higher than that in para-carcinoma tissues;the difference was statistically significant(P<0.05).The abnormal expression of PTK7 was correlated with the tumor stage,lymph node metastasis,and the vascular tumor embolus(P<0.05).The survival analysis suggested that the survival time or recurrence-free time of patients with PTK7 high expression in pancreatic duct adenocarcinoma was significantly shorter than in those with low expression(P<0.05,respectively).ShRNA interference of PTK7 was successfully established in the cell stabilizing system,verified by MTT and clone formation.Results indicated that cell survival was significantly lower in the shRNA experimental group compared to the control group(P<0.05),the number of colonies formed was significantly smaller in the shRNA experimental group compared to the control group(P<0.05),and the expression of proliferation-related proteins Ki-67 and PCNA was significantly lower in the shRNA experimental group compared to the control group(P<0.05,respectively).Conclusions:The up-regulation of PTK7 expression in pancreatic ductal adenocarcinoma tissues was associated with the tumor stage,lymph node metastasis,and the vascular tumor thrombus,suggesting poor prognosis.It was also found that in pancreatic cancer cell lines,PTK7 could promote the proliferation of pancreatic cancer cells by regulating the levels of proliferative factors Ki-67 and PCNA.