Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of <i>PPM1K</i> in the Tumor Microenvironment

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 a...

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Bibliographic Details
Main Authors: Yanyan Zhuang, Sihua Lan, Wa Zhong, Fengting Huang, Juanfei Peng, Shineng Zhang
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/2/474
Description
Summary: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, <i>PPM1K</i> was downregulated in the tissue and peripheral blood of PAAD patients, whose expression level was negatively related to poor prognosis. Further to this, <i>PPM1K</i> was found to play a role in the epithelial–mesenchymal transition and immune infiltration. ROC curves showed that <i>PPM1K</i> had a good predictive value for pancreatic adenocarcinoma. The knockdown of <i>PPM1K</i> 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 <i>PPM1K</i> in tumor immunotherapy and brings about novel insights into the prognostic value of <i>PPM1K</i> in pancreatic adenocarcinoma.
ISSN:2072-6694