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Identification of Significant Genes and Pathways in Acute Pancreatitis via Bioinformatical Analysis

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Abstract

Background and Aims

Acute pancreatitis (AP) is one of the common acute abdominal diseases with complicated pathogenesis. The purpose of this study is to identify the differentially expressed genes (DEGs) in the pancreas and underlying mechanisms.

Methods

Gene expression profiles of GSE109227 and GSE65146 were available from GEO database. Then, an integrated analysis of these genes was performed, including gene ontology (GO) and KEGG pathway enrichment analysis, protein–protein interaction (PPI) network construction, core gene correlation analysis, transcription factors (TFs) prediction, and expression level evaluation in human organs.

Results

A total number of 92 differential expressed genes were screened from the datasets, including 81 up-regulated genes and 11 down-regulated genes. The up-regulated genes were mainly enriched in the biological process, such as sarcomere organization, actin cytoskeleton organization, tumor necrosis factor biosynthetic process, response to cytokine, cell–cell adhesion, and the cell migration, and also involved in some signaling pathways, including leukocyte transendothelial migration, proteoglycans in cancer, thyroid cancer, cell adhesion, tight junction, bladder cancer, amoebiasis, glycerolipid metabolism, and VEGF signaling pathway, while down-regulated genes were significantly enriched in the endoplasmic reticulum unfolded protein response, the oxidation–reduction, and no significant signaling pathways. CDH1 and CLDN4 were identified as core genes by PPI network analysis with MCODE plug-in, as well as GO and KEGG re-enrichment. For validation in Gene Expression Profiling Interactive Analysis (GEPIA), CDH1 and CLDN4 were interacting with each other and regulated by the predictive common TFs FOXP3 or USF2. The two core genes and USF2 were expressed in varied human organs including the pancreas, while FOXP3 was not detected in the normal human pancreatic tissues.

Conclusions

This study implied that core gene CDH1 and CLDN4, which might be regulated by FOXP3 or USF2, played a significant role in acute pancreatitis. They could be potential diagnostic and therapeutic targets for AP patients.

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Funding

This work was supported by National Natural Science Foundation of China [Grant Nos. 81600501, 81670581]; Medical Guiding project of Science and Technology Commission of Shanghai Municipality [Grant number 16411970700, 18411966400]; and Key Discipline Construction Project of Shanghai Municipal Commission of Health and Family Planning [Grant Nos. 2016ZB0206].

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    Authors and Affiliations

    1. Rui** Hospital, No. 197 Rui** 2nd Road, Shanghai, 200001, China

      Ran Ji, Ying Chen, Weiwei Chen, Yuming Wang, Fangchen Gong, Shunwei Huang, Rongli **e, Ming Zhong, Zhaojun Liu, Zhitao Yang, Jian Fei, Enqiang Mao & Erzhen Chen

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    Ji, R., Chen, Y., Chen, W. et al. Identification of Significant Genes and Pathways in Acute Pancreatitis via Bioinformatical Analysis. Dig Dis Sci 66, 3045–3053 (2021). https://doi.org/10.1007/s10620-020-06598-4

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