Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2024; 15(2): 170-185
Published online Feb 15, 2024. doi: 10.4239/wjd.v15.i2.170
Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus: A pilot bioinformatics study
Han Chen, Guo-Xin Zhang, Xiao-Ying Zhou
Han Chen, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210003, Jiangsu Province, China
Guo-Xin Zhang, Xiao-Ying Zhou, Department of Gastroenterology, Jiangsu Province Hospital, Nanjing 210029, Jiangsu Province, China
Co-corresponding authors: Guo-Xin Zhang and Xiao-Ying Zhou.
Author contributions: Zhou XY and Zhang GX concepted and designed the research study; Chen H and Zhou X developed methodology; Chen H acquired the data; Zhou XY analyzed and interpretated the data; Chen H wrote the first version of the manuscript; Zhang GX and Zhou XY revised the manuscript; all authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. Zhou XY and Zhang GX contributed equally to this work as co-corresponding authors. The reasons for designating Zhou XY and Zhang GX as co-corresponding authors are threefold. First, the research was performed as a collaborative effort, and the designation of co-corresponding authorship accurately reflects the distribution of responsibilities and burdens associated with the time and effort required to complete the study and the resultant paper. This also ensures effective communication and management of post-submission matters, ultimately enhancing the paper's quality and reliability. Second, the overall research team encompassed authors with a variety of expertise and skills from different fields, and the designation of co-corresponding authors best reflects this diversity. This also promotes the most comprehensive and in-depth examination of the research topic, ultimately enriching readers' understanding by offering various expert perspectives. Third, Zhou XY and Zhang GX contributed to almost the same funding on this research. The choice of these researchers as co-corresponding authors acknowledges and respects this equal contribution, while recognizing the spirit of teamwork and collaboration of this study. In summary, we believe that designating Zhou XY and Zhang GX as co-corresponding authors of is fitting for our manuscript as it accurately reflects our team's collaborative spirit, equal contributions, and diversity.
Supported by National Natural Science Foundation of China, No. 82100594.
Institutional review board statement: The original data in this study were retrieved from the public GEO database with an open license for data use. This study was approved by the ethic committee of the First Affiliated Hospital of Nanjing Medical University (Approval No. 2022-SR-406).
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Ying Zhou, MD, PhD, Associate Chief Physician, Department of Gastroenterology, Jiangsu Province Hospital, No. 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, China. zhouxiaoying0926@njmu.edu.cn
Received: September 21, 2023
Peer-review started: September 21, 2023
First decision: November 9, 2023
Revised: November 21, 2023
Accepted: December 27, 2023
Article in press: December 27, 2023
Published online: February 15, 2024
Abstract
BACKGROUND

Helicobacter pylori (H. pylori) infection is related to various extragastric diseases including type 2 diabetes mellitus (T2DM). However, the possible mechanisms connecting H. pylori infection and T2DM remain unknown.

AIM

To explore potential molecular connections between H. pylori infection and T2DM.

METHODS

We extracted gene expression arrays from three online datasets (GSE60427, GSE27411 and GSE115601). Differentially expressed genes (DEGs) commonly present in patients with H. pylori infection and T2DM were identified. Hub genes were validated using human gastric biopsy samples. Correlations between hub genes and immune cell infiltration, miRNAs, and transcription factors (TFs) were further analyzed.

RESULTS

A total of 67 DEGs were commonly presented in patients with H. pylori infection and T2DM. Five significantly upregulated hub genes, including TLR4, ITGAM, C5AR1, FCER1G, and FCGR2A, were finally identified, all of which are closely related to immune cell infiltration. The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links. TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs, the largest number of TFs among the 5 hub genes.

CONCLUSION

We identified five hub genes that may have molecular connections between H. pylori infection and T2DM. This study provides new insights into the pathogenesis of H. pylori-induced onset of T2DM.

Keywords: Helicobacter pylori, Type 2 diabetes mellitus, Bioinformatics analysis, Differentially expressed genes, Hub genes

Core Tip: This bioinformatic research is the one of the first studies to identify the key genes and pathways associated with both Helicobacter pylori (H. pylori) infection and type 2 diabetes mellitus (T2DM), using integrated bioinformatics analyses. Five hub genes were identified, including TLR4, C5AR1, ITGAM, FCGR2A, FCER1G, and all of which were closely related to immune cell infiltration. We also verified their expression in clinical specimens. Hopefully, this study will shed some light on the pathogenesis of H. pylori-induced T2DM in the future. This study is of great clinical importance.