Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of PPM1K in the Tumor Microenvironment

SIMPLE SUMMARY: Pancreatic adenocarcinoma is a devastating disease, with an extremely poor survival rate worldwide. Its poor responsiveness to chemotherapy and immunotherapy has a bearing on the unique tumor microenvironment. Our study demonstrates that Metal-dependent protein phosphatases (PPMs) be implicated in cell–cell adhesion and immune cell infiltration in pancreatic cancer. Among these, PPM1K was downregulated in the tissue and peripheral blood of pancreatic adenocarcinoma patients, negatively related to PD-L1 expression and poor prognosis. The knockdown of PPM1K markedly promoted the proliferation and migration of pancreatic cancer cells, confirming its role in tumor suppressor activity in pancreatic adenocarcinoma. This study reveals the potential clinical utility of PPM1K in tumor immunotherapy and brings about novel insights into the prognostic value of PPM1K in pancreatic adenocarcinoma. ABSTRACT: Early metastasis and resistance to traditional therapy are responsible for the poor prognosis of pancreatic adenocarcinoma patients. Metal-dependent protein phosphatases (PPMs) have been proven to play a crucial role in the initiation and progression of various tumors. Nevertheless, the expression and function of distinct PPMs in pancreatic adenocarcinoma have not been fully elucidated. In this study, we investigated the mRNA expression level, prognostic value, and the relationship between the expression of PPMs and the tumor microenvironment in pancreatic adenocarcinoma using Oncomine, TCGA and GTEx, GEO, Kaplan–Meier plotter, STRING, GeneMANIA, and HPA databases and R packages. GO and KEGG analysis revealed that PPMs and their differential co-expression genes are attributed to cell–cell adhesion and immune cell infiltration. Among these, PPM1K was downregulated in the tissue and peripheral blood of PAAD patients, whose expression level was negatively related to poor prognosis. Further to this, PPM1K was found to play a role in the epithelial–mesenchymal transition and immune infiltration. ROC curves showed that PPM1K had a good predictive value for pancreatic adenocarcinoma. The knockdown of PPM1K markedly promoted the proliferation and migration of pancreatic cancer cells, confirming its role in tumor suppressor activity in PAAD. This study demonstrates the potential clinical utility of PPM1K in tumor immunotherapy and brings about novel insights into the prognostic value of PPM1K in pancreatic adenocarcinoma.