PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma

Abstract Background Emerging evidence has shown the crucial roles of pleomorphic adenoma gene (PLAG) family genes in multiple cancers. However, their functions and mechanisms in pancreatic adenocarcinoma (PAAD) remain poorly understood. Methods We analyzed the expression levels of PLAG family genes...

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Main Authors: Xing Liang, Zhiping Fu, Liang Tang, Minghui Zheng, Danlei Chen, Anan Liu, Ligang Shi, Linhua Yang, Chenghao Shao, Xiaoqiang Dong
Format: Article
Language:English
Published: BMC 2023-01-01
Series:BMC Gastroenterology
Subjects:
Online Access:https://doi.org/10.1186/s12876-022-02609-y
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author Xing Liang
Zhiping Fu
Liang Tang
Minghui Zheng
Danlei Chen
Anan Liu
Ligang Shi
Linhua Yang
Chenghao Shao
Xiaoqiang Dong
author_facet Xing Liang
Zhiping Fu
Liang Tang
Minghui Zheng
Danlei Chen
Anan Liu
Ligang Shi
Linhua Yang
Chenghao Shao
Xiaoqiang Dong
author_sort Xing Liang
collection DOAJ
description Abstract Background Emerging evidence has shown the crucial roles of pleomorphic adenoma gene (PLAG) family genes in multiple cancers. However, their functions and mechanisms in pancreatic adenocarcinoma (PAAD) remain poorly understood. Methods We analyzed the expression levels of PLAG family genes in both The Cancer Genome Atlas (TCGA) database and a Gene Expression Omnibus (GEO) database, and confirmed the results in our three independent cohorts of 382 PAAD tissues and 362 adjacent nontumor pancreatic tissues. Integrated analyses were carried out to explore the function, mechanism and prognostic value of the selected PLAG family gene in PAAD patients. Results By analyzing the TCGA and GEO databases, PLAGL1 was identified to be downregulated in PAAD tissues, and its decreasing levels of both mRNA and protein were verified in our three independent PAAD cohorts. PLAGL1 expression was inversely correlated with clinicopathological factors including the Ki67+ cell rate and pathologic stage. Further GSEA of the TCGA-PAAD cohort demonstrated that multiple signaling pathways implicated in cell proliferation were enriched in the lower PLAGL1 expressing PAAD group. Moreover, we demonstrated that PLAGL1 expression was obviously negatively associated with patients’ overall survival outcome in both the TCGA-PAAD cohort and our verification cohorts. Additionally, through MTS and BrdU assays, we further demonstrated in vitro that PLAGL1 had the impact of preventing the proliferation of pancreatic cancer cells. Conclusions Our present study suggested that downregulated PLAGL1 might act as a biomarker in predicts poor prognosis and one of important factors in increasing cell proliferation in PAAD. This study provides us with a novel prognostic marker and therapeutic strategy for PAAD, which deserves further study.
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spelling doaj.art-8fb41d10d93a49daac236e9f58ea60012023-01-08T12:13:28ZengBMCBMC Gastroenterology1471-230X2023-01-0123111110.1186/s12876-022-02609-yPLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinomaXing Liang0Zhiping Fu1Liang Tang2Minghui Zheng3Danlei Chen4Anan Liu5Ligang Shi6Linhua Yang7Chenghao Shao8Xiaoqiang Dong9Department of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Pancreatic-Biliary Surgery, Second Affiliated Hospital of Naval Medical UniversityDepartment of Pancreatic-Biliary Surgery, Second Affiliated Hospital of Naval Medical UniversityDepartment of Pancreatic-Biliary Surgery, Second Affiliated Hospital of Naval Medical UniversityDepartment of Pancreatic-Biliary Surgery, Second Affiliated Hospital of Naval Medical UniversityDepartment of Pancreatic-Biliary Surgery, Second Affiliated Hospital of Naval Medical UniversityDepartment of Pancreatic-Biliary Surgery, Second Affiliated Hospital of Naval Medical UniversityDepartment of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Pancreatic-Biliary Surgery, Second Affiliated Hospital of Naval Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityAbstract Background Emerging evidence has shown the crucial roles of pleomorphic adenoma gene (PLAG) family genes in multiple cancers. However, their functions and mechanisms in pancreatic adenocarcinoma (PAAD) remain poorly understood. Methods We analyzed the expression levels of PLAG family genes in both The Cancer Genome Atlas (TCGA) database and a Gene Expression Omnibus (GEO) database, and confirmed the results in our three independent cohorts of 382 PAAD tissues and 362 adjacent nontumor pancreatic tissues. Integrated analyses were carried out to explore the function, mechanism and prognostic value of the selected PLAG family gene in PAAD patients. Results By analyzing the TCGA and GEO databases, PLAGL1 was identified to be downregulated in PAAD tissues, and its decreasing levels of both mRNA and protein were verified in our three independent PAAD cohorts. PLAGL1 expression was inversely correlated with clinicopathological factors including the Ki67+ cell rate and pathologic stage. Further GSEA of the TCGA-PAAD cohort demonstrated that multiple signaling pathways implicated in cell proliferation were enriched in the lower PLAGL1 expressing PAAD group. Moreover, we demonstrated that PLAGL1 expression was obviously negatively associated with patients’ overall survival outcome in both the TCGA-PAAD cohort and our verification cohorts. Additionally, through MTS and BrdU assays, we further demonstrated in vitro that PLAGL1 had the impact of preventing the proliferation of pancreatic cancer cells. Conclusions Our present study suggested that downregulated PLAGL1 might act as a biomarker in predicts poor prognosis and one of important factors in increasing cell proliferation in PAAD. This study provides us with a novel prognostic marker and therapeutic strategy for PAAD, which deserves further study.https://doi.org/10.1186/s12876-022-02609-yPancreatic adenocarcinomaPLAGL1Cell proliferationPrognostic biomarkerOverall survival
spellingShingle Xing Liang
Zhiping Fu
Liang Tang
Minghui Zheng
Danlei Chen
Anan Liu
Ligang Shi
Linhua Yang
Chenghao Shao
Xiaoqiang Dong
PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
BMC Gastroenterology
Pancreatic adenocarcinoma
PLAGL1
Cell proliferation
Prognostic biomarker
Overall survival
title PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
title_full PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
title_fullStr PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
title_full_unstemmed PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
title_short PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
title_sort plagl1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
topic Pancreatic adenocarcinoma
PLAGL1
Cell proliferation
Prognostic biomarker
Overall survival
url https://doi.org/10.1186/s12876-022-02609-y
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