脑源性神经营养因子和酪氨酸激酶受体B在胰腺导管腺癌中的表达及其临床意义

Expression of brain-derived neurotrophic factor and tyrosine kinase B receptor in pancreatic duct cancer and its clinical significance

目的 探讨脑源性神经生长因子(BDNF)蛋白和其配体酪氨酸激酶受体(TrkB)在胰腺导管腺癌中的表达及其临床意义。方法 收集我院手术切除胰腺导管腺癌62例作为研究对象,免疫组织化学SP法检测胰腺导管腺癌神经侵犯组32例、未侵犯组30例,正常胰腺标本10例作为对照组,实时定量聚合酶链反应(Real-time PCR)和Western blot分别从基因转录水平和蛋白水平对BDNF及其配体TrkB在胰腺导管腺癌组织、癌旁组织及正常组织中的表达进行检测;数据统计学分析,比较BDNF在胰腺导管腺癌组织、癌旁组织及正常组织中的差异与临床病理相关因素之间的相关性,尤其是与嗜神经侵袭之间的相关性。 结果 胰腺导管腺癌组织中神经侵犯组BDNF阳性表达率为56.2%(18/32例)高于神经未侵犯组为30.0%(9/30例);神经侵犯组TrkB阳性表达率为62.5%(20/32例)高于未见神经侵犯组为36.7%(11/30例),而在10例正常胰腺组未见BDNF和TrkB两者阳性表达,且神经浸润组明显高于神经未浸润组(P<0.05),有淋巴结转移组明显高于无淋巴结转移组(P>0.05),邻近神经组织的癌细胞BDNF和TrkB阳性程度高于远离神经组织的癌细胞:统计分析发现,BDNF蛋白阳性率表达与肿瘤直径、肿瘤位置、神经侵犯密切相关(P<0.05);TrkB蛋白阳性率表达与肿瘤位置、神经浸润、临床分级、淋巴结转移有统计学意义(P<0.05);BDNF的mRNA表达水平在胰腺癌神经侵犯组中的表达量分别是神经未侵犯组和正常胰腺组的2.06倍和4.07倍,差异有统计学意义(P<0.05);TrkB的mRNA表达水平在胰腺癌神经侵犯组中的表达量分别是神经未侵犯组和正常胰腺组的5.41倍和1.64倍,组间比较有统计学意(P<0.05)。结论 BDNF及受体TrkB共同参与胰腺癌的发生发展,两者在胰腺癌组织中的高表达和胰腺癌嗜神经生长密切相关。

Objective To study the expression of brain-derived neurotrophic factor (BDNF) and Tyrosine Kinase B Receptor (TrkB) in pancreatic ductal adenocarcinoma (PDAC) and it’s relationship in PDAC. Methods Collected 62 cases of PDAC paraffin samples which surgical resection was performed in Anhui provincial hospital from August 2003 to December 2015. In the study, First, according to the postoperative pathology of nerve invasion into two groups in 62 cases of pancreatic cancer specimens: Perineural invasion (PNI)-positive group (32/62) and PNI-negative group (30/62), comparative analysis of the clinical pathological characteristics, especially the relationship with perineural invasion, at the same time with 10 cases of normal pancreas tissues as control, then using immunohistochemical SP method, the Real-time polymerase chain reaction (PCR)and Western blotting separately from gene transcription level and protein level of BDNF and TrkB validated positive expression in pancreatic cancer.Results PDAC nerve invasion in the group of BDNF positive expression rate was 56.2% (18/32 cases), nerve not infringe tissues was 30.0% (9/30 cases);Nerve invasion group TrkB positive expression rate was 62.5% (20/32 cases), nerve not infringe tissues was 36.7% (11/30 cases), but not seen in 10 cases of normal pancreatic tissues of BDNF and TrkB both positive expression, and nerve infiltrating group is significantly higher than without nerve infiltration (P<0.05), lymph node metastasis group were significantly higher than those without lymph node metastasis group (P>0.05), adjacent to cancer cells of the nervous tissue of BDNF and TrkB positive degree higher than cancer cells from nervous tissue;Statistical analysis found that BDNF protein positive expression and the tumor diameter, tumor location, closely related to neural invasion (P<0.05);TrkB protein positive expression and the tumor location, nerve infiltration, clinical stage, lymph node metastasis (P<0.05);BDNF mRNA expression levels in pancreatic cancer, nerve invasion in the group to express quantity are not nerve invasion and normal pancreas group 2.06 times and 4.07 times, the difference was statistically significant (P<0.05);TrkB mRNA expression levels in pancreatic cancer, nerve invasion in the group to express quantity are not nerve invasion and normal pancreas group 5.41 times and 1.64 times that of comparison between groups was statistically significant (P<0.05). Conclusion This study shows that PDAC with evidence of PNI shows increased expression of BDNF and TrkB and suggests that BDNF and TrkB are involved with the mechanism leading to PNI.