Identification Of GPSM2 As A Prognosis Biomarker Of The Pancreatic Adenocarcinoma And Exploration Of Its Regulation Mechanism

Objective:The high mortality and difficulty in diagnosis of pancreatic adenocarcinoma(PAAD)encourage us to develop a more in-depth understanding of the disease.To explore the prognostic value and physiological mechanism of G-protein signaling modulator 2(GPSM2)in PAAD.Methods:The sequencing data and clinical information of 177 samples of PAAD were recruited from The Cancer Genome Atlas(TCGA).Then the relationship between GPSM2 expression and the clinical and prognostic characteristics was analyzed.The proportion of each component in the tumor microenvironment of pancreatic cancer was analyzed through bioinformatic methods to explore its correlation with GPSM2.Subsequently,MTT,cell cycle and transwell migration assays were carried out to explore the variations of functional aspects after PANC-1 cells with stable low-expression of G-protein signaling modulator 2(GPSM2)were constructed.Downstream genes of GPSM2 were detected by microarray analysis and visualized by protein-protein interaction(PPI)network.The downstream genes of GPSM2 were verified by qRT-PCR and Western blot.Results:We described it as an independent prognostic factor in univariate and multivariate Cox regression analysis(P = 3.76E-04;P = 0.032).Also,we found that GPSM2 expression was correlated with the proportion of tumor cells(P = 0.035)and immune cells(P = 0.018)in the tumor microenvironment.Further analysis showed that GPSM2 related immune components were CD8 + T cells(P = 0.01),dendritic cells(P = 0.011)and macrophages(P < 0.001).Then after PANC-1 cells with stable low-expression of GPSM2 were constructed,MTT,cell cycle and transwell migration assays were performed and the results showed that the silencing of GPSM2 restrained the proliferation and migration of the cells(all P < 0.05).Also,we carried out the microarray analysis and 1631 differentially expressed genes(DEGs)were found.Then microarray data were adapted to the protein-protein interaction(PPI)network for annotation and visualization and several hub genes were found,such as AKT1.Finally,the relationship between GPSM2 and downstream hub genes,including ITGB1(P = 0.021),ITGB5(P < 0.001),ITGA2(P = 0.009)and ITGA5(P < 0.001),was proved by qRT-PCR.Also,western blot proved that protein levels of ITGB1 and ITGB5 also decreased significantly after GPSM2 silencing.Conclusions:GPSM2 promotes the proliferation and migration of PAAD cells and appears to be a novel prognostic factor.Targeting GPSM2 and its downstream genes may prolong the survival time of patients.