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

Xiaohua Lei; Guodong Chen; Jiangtao Li; Wu Wen; Jian Gong; Jie Fu

doi:10.7717/peerj.12141

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. 2021 Sep 6:9:e12141. doi: 10.7717/peerj.12141. eCollection 2021.

Authors

Xiaohua Lei¹, Guodong Chen¹, Jiangtao Li¹, Wu Wen¹, Jian Gong², Jie Fu³

Affiliations

¹ The First Affiliated Hospital, Department of Hepato-Biliary-Pancreatic Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
² Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

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.

Keywords: Bioinformatic analysis; FN1; I. vitro experiments; Pancreatic ductal adenocarcinoma.

Grants and funding

This work was supported by the Scientific Research Fund Project of Hunan Provincial Health Commission (20200284 and 20201919). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.