The Expression And Clinical Prognostic Value Of Protein Phosphatase 1 Catalytic Subunit Beta In Pancreatic Cancer

Objective:Pancreatic cancer（PAAD）is a common malignancy with a poor survival rate.The identification of novel biomarkers could improve clinical outcomes for patients with PAAD.Methods and Results:Here we evaluated the expression and clinical significance of PPP1CB（protein phosphatase 1 catalytic subunit beta）in PAAD.PPP1 CB expression was higher in PAAD tissue than in matched paracancerous tissue（P < 0.05）.We predicted a network of regulatory targets and protein interaction partners of PPP1 CB,and identified a P-PI network consisting of 39 node genes.The expression of 33 node genes was higher in PAAD tissue than in matching paracancerous tissue.High expression of the node genes ACTN4,ANLN,CLTB,IQGAP1,SPTAN1,and TMOD3 was associated with improved overall survival（P < 0.05）.Si RNA knockdown of PPP1 CB significantly reduced the migration,invasion and proliferation of PAAD cells.A PPP1 CB immunohistochemical staining was performed using a tissue microarray（TMA）,consisting of tumor samples collected from 91 patients with PAAD（88 of which contained matched paracancerous tissues）.The expression of PPP1 CB in PAAD was significantly higher than in the matched paracancerous tissue,（P = 0.016）.High PPP1 CB expression was associated with patient sex（P = 0.048）,alcohol use（P= 0.039）,CEA（P = 0.038）,N stage（P = 0.001）,and invasion of nerve（P = 0.036）.Furthermore,high PPP1 CB expression was associated with significantly poorer overall survival（P = 0.022）.To further analyze the specific mechanism of PPP1CB’s involvement in pancreatic cancer,we studied the relationship between PPP1 CB and epithelial-mesenchymal transformation（EMT）.Western Blot and immunofluorescence were used to detect the expression of EMT-related proteins in pancreatic cancer cells after PPP1 CB knockdown,and E-cadherin was found to be up-regulated and vimentin be reduced.It is preliminatively proved that PPP1 CB participates in the regulation of EMT,paving the way for further exploration of its regulation mechanism in the later stage.Conclusion: In summary,our data demonstrate that PPP1 CB is associated with the migration,invasion and proliferation of PAAD cells,and may be useful as an independent prognostic indicator for clinical outcome in patients with PAAD.