Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most commonly diagnosed cancers with a poor prognosis worldwide. Although the treatment of PDAC has made great progress in recent years, the therapeutic effects are still unsatisfactory. Methods. In this study, we identified differenti...

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Main Authors: Xiaohua Lei, Guodong Chen, Jiangtao Li, Wu Wen, Jian Gong, Jie Fu
Format: Article
Language:English
Published: PeerJ Inc. 2021-09-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/12141.pdf
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author Xiaohua Lei
Guodong Chen
Jiangtao Li
Wu Wen
Jian Gong
Jie Fu
author_facet Xiaohua Lei
Guodong Chen
Jiangtao Li
Wu Wen
Jian Gong
Jie Fu
author_sort Xiaohua Lei
collection DOAJ
description Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most commonly diagnosed cancers with a poor prognosis worldwide. Although the treatment of PDAC has made great progress in recent years, the therapeutic effects are still unsatisfactory. Methods. In this study, we identified differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues based on four Gene Expression Omnibus (GEO) datasets (GSE15471, GSE16515, GSE28735 and GSE71729). A protein–protein interaction (PPI) network was established to evaluate the relationship between the DEGs and to screen hub genes. The expression levels of the hub genes were further validated through the Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE and Human Protein Atlas (HPA) databases, as well as the validation GEO dataset GSE62452. Additionally, the prognostic values of the hub genes were evaluated by Kaplan–Meier plotter and the validation GEO dataset GSE62452. Finally, the mechanistic roles of the most remarkable hub genes in PDAC were examined through in vitro experiments. Results We identified the following nine hub genes by performing an integrated bioinformatics analysis: COL1A1, COL1A2, FN1, ITGA2, KRT19, LCN2, MMP9, MUC1 and VCAN. All of the hub genes were significantly upregulated in PDAC tissues compared with normal pancreatic tissues. Two hub genes (FN1 and ITGA2) were associated with poor overall survival (OS) rates in PDAC patients. Finally, in vitro experiments indicated that FN1 plays vital roles in PDAC cell proliferation, colony formation, apoptosis and the cell cycle. Conclusions In summary, we identified two hub genes that are associated with the expression and prognosis of PDAC. The oncogenic role of FN1 in PDAC was first illustrated by performing an integrated bioinformatic analysis and in vitro experiments. Our results provide a fundamental contribution for further research aimed finding novel therapeutic targets for overcoming PDAC.
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spelling doaj.art-994ae8a5d9d649958eac30e280c5e3512023-12-03T10:23:19ZengPeerJ Inc.PeerJ2167-83592021-09-019e1214110.7717/peerj.12141Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experimentsXiaohua Lei0Guodong Chen1Jiangtao Li2Wu Wen3Jian Gong4Jie Fu5The First Affiliated Hospital, Department of Hepato-Biliary-Pancreatic Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaThe First Affiliated Hospital, Department of Hepato-Biliary-Pancreatic Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaThe First Affiliated Hospital, Department of Hepato-Biliary-Pancreatic Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaThe First Affiliated Hospital, Department of Hepato-Biliary-Pancreatic Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaBackground Pancreatic ductal adenocarcinoma (PDAC) is one of the most commonly diagnosed cancers with a poor prognosis worldwide. Although the treatment of PDAC has made great progress in recent years, the therapeutic effects are still unsatisfactory. Methods. In this study, we identified differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues based on four Gene Expression Omnibus (GEO) datasets (GSE15471, GSE16515, GSE28735 and GSE71729). A protein–protein interaction (PPI) network was established to evaluate the relationship between the DEGs and to screen hub genes. The expression levels of the hub genes were further validated through the Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE and Human Protein Atlas (HPA) databases, as well as the validation GEO dataset GSE62452. Additionally, the prognostic values of the hub genes were evaluated by Kaplan–Meier plotter and the validation GEO dataset GSE62452. Finally, the mechanistic roles of the most remarkable hub genes in PDAC were examined through in vitro experiments. Results We identified the following nine hub genes by performing an integrated bioinformatics analysis: COL1A1, COL1A2, FN1, ITGA2, KRT19, LCN2, MMP9, MUC1 and VCAN. All of the hub genes were significantly upregulated in PDAC tissues compared with normal pancreatic tissues. Two hub genes (FN1 and ITGA2) were associated with poor overall survival (OS) rates in PDAC patients. Finally, in vitro experiments indicated that FN1 plays vital roles in PDAC cell proliferation, colony formation, apoptosis and the cell cycle. Conclusions In summary, we identified two hub genes that are associated with the expression and prognosis of PDAC. The oncogenic role of FN1 in PDAC was first illustrated by performing an integrated bioinformatic analysis and in vitro experiments. Our results provide a fundamental contribution for further research aimed finding novel therapeutic targets for overcoming PDAC.https://peerj.com/articles/12141.pdfPancreatic ductal adenocarcinomaFN1Bioinformatic analysisI. vitro experiments
spellingShingle Xiaohua Lei
Guodong Chen
Jiangtao Li
Wu Wen
Jian Gong
Jie Fu
Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments
PeerJ
Pancreatic ductal adenocarcinoma
FN1
Bioinformatic analysis
I. vitro experiments
title Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments
title_full Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments
title_fullStr Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments
title_full_unstemmed Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments
title_short Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments
title_sort comprehensive analysis of abnormal expression prognostic value and oncogenic role of the hub gene fn1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments
topic Pancreatic ductal adenocarcinoma
FN1
Bioinformatic analysis
I. vitro experiments
url https://peerj.com/articles/12141.pdf
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