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The Research Of The Role Of Stat1in The Advance Of Pancreatic Cancer

Posted on:2015-12-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y SunFull Text:PDF
GTID:1224330431978285Subject:Surgery
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ObjectiveThe transcription factor Statl is a member of the family of signal transducers and transcription activators and responds to interferon-stimulation. The aim of this study was to analyze Statl expression for prediction of pancreatic cancer progression and prognosis.Methods1. A total of100pancreatic adenocarcinoma tissue specimens were used for constru-ction of a pancreatic cancer tissue microarray (TMA) for immunohistochemical stai-ning of Statl and p21expression.2. Silence Statl gene in BxPC-3cells by transferred Statl-specific siRNAs. The effect of STAT1silencing on the levels of VEGF, MMP2, MMP9expression was determined by western blot assays. The migrate ability was detected by transwell assay.Resultsl.Statl and p21proteins were expressed in88%(88/100) and82%(82/100) of pancreatic adenocarcinoma tissue specimens, and expression was inversely associated with tumor differentiation, clinical stages, and lymph node metastasis of pancreatic cancer. There was no association with age, tumor size or invasion. Moreover, Kaplan-Meier curve analysis showed that patients with higher Statl and p21expression had better overall survival rates than those with low expression of Statl and p21proteins.2. The plasid Statl-siRNA and siRNA was transferred to BxPC-3cells successful. Western blot revealed the levels of VEGF, MMP2and MMP9expression in the si STAT1group was significantly higher than levels in the Statl group. The migrate ability in si-Statl group was higher than other groups. The proliferation in si-Statl group was higher than other groups.Conclusions1.The expression of Statl and P21proteins was positively correlated (co-expressed in tumor cells), whereas the loss of expression of Statl and p21proteins was associated with tumor de-differentiation, advanced clinical stages, and lymph node metastasis of pancreatic cancer. There was no association between age and tumor size or invasion. The loss of Stat1and p21expression was also associated with poor overall survival of pancreatic adenocarcinoma patients. This study suggests that Statl and p21proteins could be further evaluated as biomarkers for predicting pancreatic adenocarcinoma progression and prognosis2. It was found that the proliferation an migration was improved in cells that statl was silenced. This found proved the study results in pancreatic adenocarcinoma tissue specimens tested by immunohistochemistry. The levels of VEGF, MMP2and MMP9expression in the si-STAT1group was significantly higher than levels in the Statl group, which means loss of Statl expression regulate the process of pancreatic cancer via increasing the expression of VEGF, MMP2and MMP9possibly.
Keywords/Search Tags:Stat1, P21, VEGF, MMP2, MMP9, Gene Silencing Western-blottingTranswell
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