Journal of Inflammation Research (Apr 2023)
Construction of the Interaction Network of Hub Genes in the Progression of Barrett’s Esophagus to Esophageal Adenocarcinoma
Abstract
Kai Li,1,2,* Peipei Duan,1,2,* Haifa He,3,* Ruijuan Du,1,2 Qian Wang,1,2 Pengju Gong,4 Hua Bian1 1Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Nanyang, Henan, People’s Republic of China; 2Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation, Nanyang Institute of Technology, Nanyang, Henan, People’s Republic of China; 3Department of Pathology, Nanyang Central Hospital, Nanyang, Henan, People’s Republic of China; 4The University of Texas MD Anderson Cancer Center UThealth Graduate School of Biomedical Sciences, Houston, TX, USA*These authors contributed equally to this workCorrespondence: Hua Bian; Kai Li, Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, No. 80 Changjiang Road, Wancheng District, Nanyang, Henan, People’s Republic of China, Email [email protected]; [email protected]: Esophageal adenocarcinoma (EAC) is one of the histologic types of esophageal cancer with a poor prognosis. The majority of EAC originate from Barrett’s esophagus (BE). There are few studies focusing on the dynamic progression of BE to EAC.Methods: R software was used to analyze differentially expressed genes (DEGs) based on RNA-seq data of 94 normal esophageal squamous epithelial (NE) tissues, 113 BE tissues and 147 EAC tissues. The overlapping genes of DEGs between BE and EAC were analyzed by Venn diagram tool. The hub genes were selected by Cytoscape software based on the protein-protein interaction network of the overlapping genes using STRING database. The functional analysis of hub genes was performed by R software and the protein expression was identified by immunohistochemistry.Results: In the present study, we found a large degree of genetic similarity between BE and EAC, and further identified seven hub genes (including COL1A1, TGFBI, MMP1, COL4A1, NID2, MMP12, CXCL1) which were all progressively upregulated in the progression of NE-BE-EAC. We have preliminarily uncovered the probable molecular mechanisms of these hub genes in disease development and constructed the ceRNA regulatory network of hub genes. More importantly, we explored the possibility of hub genes as biomarkers in the disease progression of NE-BE-EAC. For example, TGFBI can be used as biomarkers to predict the prognosis of EAC patients. COL1A1, NID2 and COL4A1 can be used as biomarkers to predict the response to immune checkpoint blockade (ICB) therapy. We also constructed a disease progression risk model for NE-BE-EAC based on CXCL1, MMP1 and TGFBI. Finally, the results of drug sensitivity analysis based on hub genes showed that drugs such as PI3K inhibitor TGX221, bleomycin, PKC inhibitor Midostaurin, Bcr-Abl inhibitor Dasatinib, HSP90 inhibitor 17-AAG, and Docetaxel may be potential candidates to inhibit the progression of BE to EAC.Conclusion: This study is based on a large number of clinical samples with high credibility, which is useful for revealing the probable carcinogenic mechanism of BE to EAC and developing new clinical treatment strategies.Keywords: Barrett’s esophagus, esophageal adenocarcinoma, hub genes, carcinogenic mechanism, biomarker
