The Prognostic Significance and Tumor-promoting Roles of MED30 in Pancreatic Cancer

Background: MED30 is an evolutionarily new member of the mediator complex thatcan bridge transcription factors and preinitiation complexfor the transcription. Pancreatic cancer is highly chemo-resistant andis the fourth leading cause of cancer-related deaths. Rapid progression and poor prognosis of pancreatic cancer result in shortened survival rate following diagnosis. Methods: Expression of MED30 was investigated by the analysis of TCGA database and immunohistochemistry of patients tissues. Roles of MED30 were investigated by gain-of-function and loss-of-function studies. Results: Analysis of TCGA database and immunohistochemistry provedthe frequentamplification and overexpression of MED30 in the pancreatic cancer tissues compared with the normal pancreatic tissues at the chromosome, mRNA and protein levels. Notably its overexpression was association with poor prognosis of pancreatic cancer patients in the Kaplan-Meier curve analysis ( P =0.00072) and multivariate analysis ( P =0.027). Uno’s C-index values in the time-dependent Area Under the Curve (AUC) analysis and AUC valuein the receiver operating characteristics (ROC) curves showed its good performance as a prognostic marker. To reveal the functional roles of MED30 during the progression of pancreatic cancer, we overexpressed or knocked down MED30 using cDNA or siRNA, respectively. Gain-of-function and loss-of-function studies showed that MED30 can regulate proliferation, migration, and invasion of pancreatic cancer cells. Furthermore overexpression of MED30 promoted tumorigenicity in SCID mice significantly. Conclusions: MED30 is frequently amplified and overexpressed and its overexpression is associated with poor prognosis of pancreatic cancer patients. Moreover it has tumor-promoting roles in proliferation, migration, invasion and in vivo tumorigenicity of pancreatic cancer cells. Thus, MED30 could be a potent diagnostic and therapeutic target in pancreatic cancer.