Identification and Validation of Hub Genes in Acute Pancreatitis and Hypertriglyceridemia

Abstract

Background

The pathogenesis of acute pancreatitis (AP) and the relationship between acute pancreatitis and hypertriglyceridemia are complex and not fully understood. The purpose of this study was to identify the hub genes along with common differentially expressed genes (DEGs) between acute pancreatitis and hypertriglyceridemia.

Methods

We downloaded three gene expression profiles of AP and one gene expression profile of hypertriglyceridemia from the Gene Expression Omnibus (GEO) database and filtered the DEGs based on the above four datasets. Next, we identified the hub genes by performing the Gene Ontology (GO) term analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein–protein interaction (PPI) construction. We also constructed the miRNA-hub gene network and established mouse models with hypertriglyceridemia and AP using a high-fat diet and injection of caerulein (CAE), respectively. Finally, the immunohistochemical analysis was used to verify the differential expressions of hub genes in AP, hypertriglyceridemia, and normal pancreatic tissue.

Results

A total of 105 DEGs associated with AP and 149 DEGs associated with hypertriglyceridemia were identified. Additionally, we identified six hub genes of AP, all of which were closely related to the cytoskeleton while two DEGs genes were common in both AP and hypertriglyceridemia. We also verified their expression in mouse models. Finally, a network of miRNA-mRNA was also constructed, and the top seven interactive miRNAs (hsa-mir-1–3p, hsa-mir-5195–3p, hsa-mir-145–5p, hsa-let-7b-5p, hsa-mir-10b-5p, hsa-mir-206, and hsa-mir-613) targeting the most hub genes were identified.

Conclusion

Overall, we identified six hub genes associated with AP and two common DEGs associated with AP and hypertriglyceridemia along with seven miRNAs that may regulate AP. This study could provide new ideas for further elucidation of the pathogenesis of hypertriglyceridemia-induced acute pancreatitis in the future.

Keywords:

• acute pancreatitis
• biomarkers
• hypertriglyceridemia-induced pancreatitis
• bioinformatics

Data Sharing Statement

All data in the study is available from the submitting author, Shiyu Zhang.

Ethics Approval

The study has been approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (No. 2021 KY-E-187), and followed the principles of ethical animal research outlined in the Basel Declaration and the ethical guidelines of the International Council for Laboratory Animal Science (ICLAS).

Consent for Publication

All authors agree to the publication of all texts, images and tables in this study.

Disclosure

All authors report no conflicts of interest for this work and state that there is no potential conflict of interest in this research.

Additional information

Funding

All funding for this study was provided by the National Natural Science Foundation of China (81970558) and Guangxi Natural Science Foundation (2020GXNSFAA259095).