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Objective@#To investigate the expression of KLK7 in pancreatic cancer and its clinical significance.@*Methods@#Immunohistochemistry 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.@*Results@#The 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).@*Conclusions@#The 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.
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Objective@#To test the expression of miR-1178 in pancreatic cancer and study its clinicopathological significance and mechanism.@*Methods@#The expression of miR-1178 in 87 paired paraffin pancreatic ductal adenocarcinoma specimens and adjacent non- cancerous pancreatic tissue diagnosed by Pathology Department of Peking Union Medical College Hospital was detected by hybridization in situ. The relationship between the expression of miR-1178 and clinicopathological characters was analyzed.miR-1178 mimics and inhibitor were used to further detect the close relationship among miR-1178 and cancer invasion. Establish a nude mice subcutaneously transplanted tumor model, 4 weeks after vaccination for tumor volume and weight measurement.Student t-test, rank sum test, and χ2 test was used respectively to compare the data between two groups. Cox regression was adopted to improve the single factor and multiple factors analysis.@*Results@#The results of hybridization in situ showed the expression of miR-1178 was increased in 72 cases with pancreatic cancer compared to that in paired normal pancreatic tissues (50/72 vs. 11/72, χ2=43.26, P<0.05). miR-1178 expression was positively associated with tumor lymph node stage (χ2=4.189, P=0.041). Univariate and multivariate analysis revealed that miR-1178 was an independent adverse prognostic indicator for patients with pancreatic cancer (HR=2.364, 95%CI: 1.114-5.019, P=0.025). Transwell assay indicated the over-expression of miR-1178 increased the number of AsPC-1 cells that penetrated the ECM-coated membrane (177.0±19.8 vs. 119.7±15.9)(χ2=8.21, P<0.05). For the in vivo experiment, overexpression of miR-1178 significantly promoted tumor growth, compared with control group (tumor volume: (5 122.4±760.2)mm3 vs. (1 976.8±601.8)mm3, t=2.413, P<0.05; tumor weight: (1.55±0.21)g vs. (0.67±0.17)g, t=2.960, P<0.05). Over-expression of miR-1178 down-regulated the expression of Stub1 and elevated the expression of FAK/MMP-9 signal pathway(P<0.05).@*Conclusions@#MiR-1178 is overexpressed in pancreatic cancer, and is effective for predicting patients′ prognosis. MiR-1178 regulate Stub1/FAK/MMP-9 signal pathway and promote the invasion of AsPC-1 cells.
ABSTRACT
Pancreatic cancer is a one of the most malignant digestive cancer.Because the lack of effective methods for early diagnosis,most patients have been ineligible for surgical resection when diagnosed.Kallikrein family is a group of serine proteases,because of its ability to decompose the extracellular matrix proteins,it may be closely related to the invasion and metastasis of various cancers.And some members of kallikrein family may become cancer diagnostic biomarkers.This paper reviews all the recent articles about kallikrein family study in pancreatic cancer.