KLK7在胰腺癌中的表达及其对胰腺癌细胞生物学行为的影响

The expression of KLK7 in pancreatic cancer and the effects on the biological behavior of pancreatic cancer cells

目的探讨KLK7在胰腺癌中的表达及其临床意义。方法采用免疫组织化学方法检测92例胰腺癌组织芯片中KLK7的表达水平。分析KLK7与胰腺癌患者临床病理资料及预后的关系，统计学分析采用秩和检验、χ2检验、Logistic回归分析等方法。通过慢病毒载体建立KLK7稳定过表达的胰腺癌细胞株，采用KLK7-siRNA转染胰腺癌细胞株敲低KLK7; CCK-8法检测细胞增殖能力、化疗敏感性；Transwell法检测细胞侵袭和迁移能力。同时建立裸鼠皮下移植瘤模型，观察KLK7在裸鼠体内对肿瘤生长的影响。结果KLK7在胰腺癌组织中的表达水平高于癌旁组织（P〈0.05）。KLK7表达水平与脉管侵犯有相关性（χ2＝7.535，P〈0.05）；单因素及多因素分析结果发现，KLK7表达水平是影响胰腺癌脉管侵犯的独立危险因素（χ2＝7.535，P〈0.05）。在胰腺癌细胞株BxPC-3和CFPAC中过表达KLK7可以促进胰腺癌细胞增殖，降低化疗敏感性，促进其迁移和侵袭能力；降低KLK7的表达水平结果相反。体内实验结果提示，稳定过表达KLK7的胰腺癌裸鼠皮下移植瘤体积大于对照组（t＝4.479，P〈0.05）；过表达KLK7组肿瘤重量大于对照组（t＝2.831，P〈0.05）。结论KLK7在胰腺导管腺癌组织中呈高表达，是胰腺癌脉管侵犯的独立危险因素；KLK7可促进胰腺癌增殖，降低化疗敏感性，增加胰腺癌细胞侵袭迁移能力。

ObjectiveTo investigate the expression of KLK7 in pancreatic cancer and its clinical significance.MethodsImmunohistochemistry was used to detect the expression of KLK7 protein in pancreatic cancer tissue microarray with 92 samples. Statistical analysis of the relationship between KLK7 and clinicopathological characteristics was finished. Pancreatic cancer cell lines were infected with lentiviuses in order to get cells with KLK7 stable overexpression.KLK7-siRNA was transfected into pancreatic cancer cells to knock down KLK7.Cell proliferation and chemosensitivity were detected by CCK-8 assay; Cell invasion and migration abilities were detected by Transwell assay. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of KLK7 on tumor growth in nude mice. Data were statistically analyzed by rank sum test, χ2 test and Logistic regression analysis.ResultsThe expression level of KLK7 in pancreatic cancer tissues was higher than that in paired adjacent tissues （P〈0.05）. KLK7 expression was correlated with vascular invasion（χ2=7.535, P〈0.05）. Further univariate and multivariate analysis showed that KLK7 expression was an independent risk factor for vascular invasion of pancreatic cancer（χ2=7.535, P〈0.05）. The overexpression of KLK7 in pancreatic cancer cell lines BxPC-3 and CFPAC can increase their proliferation abilities, reduce the chemosensitivity and promote their migration and invasion behaviour; The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing KLK7 group was significantly larger than that in the control group （t=4.479, P〈0.05）. The group of overexpressing KLK7 showed greater tumor weight than the control group（t=2.831, P〈0.05）.ConclusionsThe expression level of KLK7 in pancreatic ductal adenocarcinoma was higher than that in paired adjacent tissues and it is an independent risk factor for vascular invasion of pancreatic cancer.KLK7 can promote the proliferation of pancreatic cancer cells, reduce the chemosensitivity and increase the invasion and migration of pancreatic cancer cells.