Identification of prognostic risk factors for pancreatic cancer using bioinformatics analysis

Dandan Jin; Yujie Jiao; Jie Ji; Wei Jiang; Wenkai Ni; Yingcheng Wu; Runzhou Ni; Cuihua Lu; Lishuai Qu; Hongbing Ni; Jinxia Liu; Weisong Xu; MingBing Xiao

doi:10.7717/peerj.9301

Identification of prognostic risk factors for pancreatic cancer using bioinformatics analysis

PeerJ. 2020 Jun 15:8:e9301. doi: 10.7717/peerj.9301. eCollection 2020.

Authors

Dandan Jin^#^{1

2}, Yujie Jiao^#^{1

2}, Jie Ji^{1

2}, Wei Jiang³, Wenkai Ni¹, Yingcheng Wu², Runzhou Ni¹, Cuihua Lu¹, Lishuai Qu¹, Hongbing Ni¹, Jinxia Liu¹, Weisong Xu⁴, MingBing Xiao^{1

5}

Affiliations

¹ Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.
² Clinical Medicine, Medical College, Nantong University, Nantong, China.
³ Department of Emergency, Affiliated Hospital of Nantong University, Nantong, China.
⁴ Department of Gastroenterology, Second People's Hospital of Nantong, Nantong, China.
⁵ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.

^# Contributed equally.

Abstract

Background: Pancreatic cancer is one of the most common malignant cancers worldwide. Currently, the pathogenesis of pancreatic cancer remains unclear; thus, it is necessary to explore its precise molecular mechanisms.

Methods: To identify candidate genes involved in the tumorigenesis and proliferation of pancreatic cancer, the microarray datasets GSE32676, GSE15471 and GSE71989 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between Pancreatic ductal adenocarcinoma (PDAC) and nonmalignant samples were screened by GEO2R. The Database for Annotation Visualization and Integrated Discovery (DAVID) online tool was used to obtain a synthetic set of functional annotation information for the DEGs. A PPI network of the DEGs was established using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and a combination of more than 0.4 was considered statistically significant for the PPI. Subsequently, we visualized the PPI network using Cytoscape. Functional module analysis was then performed using Molecular Complex Detection (MCODE). Genes with a degree ≥10 were chosen as hub genes, and pathways of the hub genes were visualized using ClueGO and CluePedia. Additionally, GenCLiP 2.0 was used to explore interactions of hub genes. The Literature Mining Gene Networks module was applied to explore the cocitation of hub genes. The Cytoscape plugin iRegulon was employed to analyze transcription factors regulating the hub genes. Furthermore, the expression levels of the 13 hub genes in pancreatic cancer tissues and normal samples were validated using the Gene Expression Profiling Interactive Analysis (GEPIA) platform. Moreover, overall survival and disease-free survival analyses according to the expression of hub genes were performed using Kaplan-Meier curve analysis in the cBioPortal online platform. The relationship between expression level and tumor grade was analyzed using the online database Oncomine. Lastly, the eight snap-frozen tumorous and adjacent noncancerous adjacent tissues of pancreatic cancer patients used to detect the CDK1 and CEP55 protein levels by western blot.

Conclusions: Altogether, the DEGs and hub genes identified in this work can help uncover the molecular mechanisms underlying the tumorigenesis of pancreatic cancer and provide potential targets for the diagnosis and treatment of this disease.

Keywords: Bioinformatics; Hub genes; Microarray analysis.

Grants and funding

This study was supported by grants from the Natural Science Foundation of China (grant No. 81472272 and 81602114), the Key Research and Development Plan of Jiangsu Province (no. BE2019692), the Postdoctoral Science Foundation of China (grant No. 2017M620221), the Social Development Foundation of Nantong City (grant no. MS22018006, MS12019018, MS12019020, JC2019032), and the Teaching Research Project of Affiliated Hospital of Nantong University (Tfj 18006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.