The Effect And Part Mechanism Studies Of Rab27A Rab27B And TP53 In Pancreatic Cancer

Pancreatic carcinoma is a common malignancy of digestive system with high malignant degree, low early diagnosis rate, rapid progression and poor prognisis. Pancreatic carcinoma has become a major diagnostic and therapeutic problem faced by the domestic and international medical profession,thus strengthening the comprehensive treatment and to explore new diagnostic biomark and therapeutic strategies is of great significance.The activities of organism cells depend on targetting proper molecules to reasonable position at the appropriate time.This important role mainly depends on vesicle transport. The dysfunction of vesicle transport may lead to a variety of organelles defects and cellular dysfunction, and is also related to tumor development. In effect molecules associated with vesicles transport,Rab protein is a member of Ras related small GTPases super family. These proteins have specific subcellular localization,and plays an important role in the process of cellular secretion, endocytosis,signal transduction and development etc. Studies have shown that Rab27 A and Rab27 B which belong to the Rab subfamily,has close relationship with the occurrence and metastasis of tumor.Some scholars found that Rab27 A is associated with the invasion and metastasis of human breast cancer cell.Rab27 B can regulate invasive growth and metastasis of estrogen receptor positive breast cancer cell. Rab27 B and Rab27 A is associated with the progress of hepatocellular carcinoma and may be a significant prognostic mark.The relationship between Rab27 and pancreatic carcinoma has not been reported.We determined protein expression of Rab27 A and TP53 and their clinical significance in 265 pancreatic tissues(186 carcinomas, 54 normal and 25 benign tissues) by immunohistochemistry analysis on tissue microarray. We found that Rab27 A and TP53 protein expression was significantly higher in cancerous tissues compared to normal and benign tissues. High Rab27 A protein expression(Rab27A+) and TP53 protein expression was significantly associated with tumor stage and distant metastasis. High expression of Rab27 A also have close relationship with vascular invasion. No correlation between Rab27 A and TP53 expression was observed. In both univariate analysis and multivariate analysis, we found that high Rab27 A expression and high TP53 expression were significantly associated with patients’ poor overall survival and poor prognosis.Our data do not support the hypothesis that TP53 regulates exosome secretion in pancreatic carcinoma through Rab27 A, but could not rule out the possibility of weak or indirect interaction between Rab27 A and TP53.In the subsequent research, to continue using immunohistochemical method, using tissue microarray technology. In the 186 cases of pancreatic cancer, 51 cases corresponding to the surrounding tissue adjacent to carcinoma and 23 cases of pancreatic benign lesions, The expression of Rab27 B and TP53 protein in tissue samples is tested, the results show that high Rab27 B protein expression can be used as independent prognostic factor in patients with pancreatic cancer. By single factor and multiple factors analysis, we found that increased expression level of Rab27 B is an important risk factor for poor prognosis of pancreatic cancer, and the increased Rab27 B and TP53 protein expression in the pancreatic cancer has close relationship with vascular invasion and distant metastasis. At the same time, we detect that Rab27 B have a significant relationship between TP53 protein, but the relationship between TP53 and Rab27 B remains to be further research.We have constructed the Rab27 A and Rab27 B siRNA, respectively, by the method of liposome transfection, in pancreatic cancer on a cellular level, respectively use such as CCK-8, Transwell little room, and Western Blot methods to test the impact on cell biological characteristics before and after transfection. Results show that decreased Rab27 A and Rab27 B gene expression inhibits the proliferation of pancreatic cancer cells, reduce the ability of invasion and metastasis, and can induce apoptosis. Besides,it have an effect of reverse regulation of the proliferation and metastasis actions of pancreatic cancer.Above all,this research first report that both Rab27 A and TP53 protein expressions were significantly higher in cancerous tissues than in normal and benign tissues,and high Rab27 A protein expression was also associated with poor prognosis.Though there’s no statistical significance of Rab27 B expressions in cancerous tissues,normal and benign tissues, five years survival rate is obviously reduced in patients with pancreatic carcinoma the high expression of Rab27 B.This research did not find significant correlation between the Rab27 A and TP53,but there were significant between Rab27 B and TP53.The specific way they interact remains to be further studied.Using siRNA interference technology in Rab27 A and Rab27 B could significantly reduce proliferation,invasion,migration ability and induce apoptosis of pancreatic cancer cell.This provide the experimental basis and theoretical basis of molecular targeted therapy.