Investigation Of The Co-relation Between GEP100 Expression And Pancreatic Ductal Adenocarcinoma Perineural Invasion And The Underlying Mechanism

Background and purpose:The pancreatic ductal adenocarcinoma(PDAC)whose morbidity is gradually increasing over past years,has low 5-year survival rates(<5%).For early and resectable PDAC patients,surgery with post-operative chemotherapy is the most effective treatment,but the recurrence rate is high.Peripheral nerve invasion(PNI)occurs in all of the PDAC,makes one of the main reasons for postoperative recurrent and metastasis,is one of the hallmark pathologic changes of pancreatic cancer cells(PCs).It is very important to investigate the mechanism of PNI in PDAC for its postoperative treatment and prevention of recurrence.This study explored the role of GEP100 in the PNI of PCs and the possible mechanisms.Materials and methods:Firstly,we detected the correlation between GEP100 and PNI using pancreatic cancer tissue samples.We transferred 47 cases between year 2013 and 2017 of PDAC from the Second Affiliated Hospital of Zhejiang University.Each case had WHIPPLE excise operation,is pathologically diagnosed of PDAC and detailed in clinical information.We used immunohistochemistry technology to mark GEP100,and analyzed the correlation between GEP100 intensity and PNI in pancreatic cancer by using statistical methods.Secondly,we used Western Blot and PT-PCR to detect GEP100 and m RNA in different pancreatic cancer cell lines,and selected Panc-1 to be the experimental cell line.We utilized sh RNA to knockdown GEP100 of Panc-1,established the co-culture model of pancreatic cancer cells(PCs)and dorsal root ganglion(DRG)in mice,and used the model to detect the effect of GEP100 on the dorsal root ganglion migration of PCs.We detected the effect of knockdown-GEP100 on exosome secretion.Conclusions:The GEP100 intensity was positively correlated with PNI level in PDAC.GEP100 knockdown inhibited the migration of pancreatic cancer cells to DRG in mice and inhibited exosome secretion in pancreatic cancer cells.Results:The GEP100 intensity was positively correlated with PNI level in PDACs.Knocking down GEP100 inhibited the ability of PDACs to migrate to nerve cells,the mechanism is possibly to inhibit exosome secretion.