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...

Full description

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
_version_ 1797444790252470272
author Yanyan Zhuang
Sihua Lan
Wa Zhong
Fengting Huang
Juanfei Peng
Shineng Zhang
author_facet Yanyan Zhuang
Sihua Lan
Wa Zhong
Fengting Huang
Juanfei Peng
Shineng Zhang
author_sort Yanyan Zhuang
collection DOAJ
description 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.
first_indexed 2024-03-09T13:17:38Z
format Article
id doaj.art-960646afc2db459083a3a12814ee566c
institution Directory Open Access Journal
issn 2072-6694
language English
last_indexed 2024-03-09T13:17:38Z
publishDate 2023-01-01
publisher MDPI AG
record_format Article
series Cancers
spelling doaj.art-960646afc2db459083a3a12814ee566c2023-11-30T21:34:24ZengMDPI AGCancers2072-66942023-01-0115247410.3390/cancers15020474Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of <i>PPM1K</i> in the Tumor MicroenvironmentYanyan Zhuang0Sihua Lan1Wa Zhong2Fengting Huang3Juanfei Peng4Shineng Zhang5Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaDepartment of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, Yanjiangxi Road, Guangzhou 510120, ChinaDepartment of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, Yanjiangxi Road, Guangzhou 510120, ChinaDepartment of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, Yanjiangxi Road, Guangzhou 510120, ChinaDepartment of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107, Yanjiangxi Road, Guangzhou 510120, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, ChinaEarly 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.https://www.mdpi.com/2072-6694/15/2/474bioinformatics analysismetal-dependent protein phosphatasespancreatic adenocarcinomaprognostic valuetumor microenvironment
spellingShingle Yanyan Zhuang
Sihua Lan
Wa Zhong
Fengting Huang
Juanfei Peng
Shineng Zhang
Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of <i>PPM1K</i> in the Tumor Microenvironment
Cancers
bioinformatics analysis
metal-dependent protein phosphatases
pancreatic adenocarcinoma
prognostic value
tumor microenvironment
title Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of <i>PPM1K</i> in the Tumor Microenvironment
title_full Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of <i>PPM1K</i> in the Tumor Microenvironment
title_fullStr Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of <i>PPM1K</i> in the Tumor Microenvironment
title_full_unstemmed Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of <i>PPM1K</i> in the Tumor Microenvironment
title_short Comprehensive Analysis of PPMs in Pancreatic Adenocarcinoma Indicates the Value of <i>PPM1K</i> in the Tumor Microenvironment
title_sort comprehensive analysis of ppms in pancreatic adenocarcinoma indicates the value of i ppm1k i in the tumor microenvironment
topic bioinformatics analysis
metal-dependent protein phosphatases
pancreatic adenocarcinoma
prognostic value
tumor microenvironment
url https://www.mdpi.com/2072-6694/15/2/474
work_keys_str_mv AT yanyanzhuang comprehensiveanalysisofppmsinpancreaticadenocarcinomaindicatesthevalueofippm1kiinthetumormicroenvironment
AT sihualan comprehensiveanalysisofppmsinpancreaticadenocarcinomaindicatesthevalueofippm1kiinthetumormicroenvironment
AT wazhong comprehensiveanalysisofppmsinpancreaticadenocarcinomaindicatesthevalueofippm1kiinthetumormicroenvironment
AT fengtinghuang comprehensiveanalysisofppmsinpancreaticadenocarcinomaindicatesthevalueofippm1kiinthetumormicroenvironment
AT juanfeipeng comprehensiveanalysisofppmsinpancreaticadenocarcinomaindicatesthevalueofippm1kiinthetumormicroenvironment
AT shinengzhang comprehensiveanalysisofppmsinpancreaticadenocarcinomaindicatesthevalueofippm1kiinthetumormicroenvironment