Identification of DEGs and transcription factors involved in H. pylori-associated inflammation and their relevance with gastric cancer

Honghao Yin; Aining Chu; Songyi Liu; Yuan Yuan; Yuehua Gong

doi:10.7717/peerj.9223

Identification of DEGs and transcription factors involved in H. pylori-associated inflammation and their relevance with gastric cancer

PeerJ. 2020 Jun 3:8:e9223. doi: 10.7717/peerj.9223. eCollection 2020.

Authors

Honghao Yin^{1

2

3}, Aining Chu^{1

2

3}, Songyi Liu^{1

2

3}, Yuan Yuan^{1

2

3}, Yuehua Gong^{1

2

3}

Affiliations

¹ Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Hospital of China Medical University, Shenyang, LiaoNing, China.
² Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, LiaoNing, China.
³ Key Laboratory of GI Cancer Etiology and Prevention in Liaoning Province, the First Hospital of China Medical University, Shenyang, LiaoNing, China.

Abstract

Background: Previous studies have indicated that chronic inflammation linked to H. pylori infection is the leading causes for gastric cancer (GC). However, the exact mechanism is not entirely clear until now.

Purpose: To identify the key molecules and TFs involved in H. pylori infection and to provide new insights into H. pylori-associated carcinogenesis and lay the groundwork for the prevention of GC.

Results: GO and KEGG analysis revealed that the DEGs of Hp⁺-NAG were mainly associated with the immune response, chemokine activity, extracellular region and rheumatoid arthritis pathway. The DEGs of Hp⁺-AG-IM were related to the apical plasma membrane, intestinal cholesterol absorption, transporter activity and fat digestion and absorption pathway. In Hp⁺-NAG network, the expression of TNF, CXCL8, MMP9, CXCL9, CXCL1, CCL20, CTLA4, CXCL2, C3, SAA1 and FOXP3, JUN had statistical significance between normal and cancer in TCGA database. In Hp⁺-AG-IM network the expression of APOA4, GCG, CYP3A4, XPNPEP2 and FOXP3, JUN were statistically different in the comparison of normal and cancer in TCGA database. FOXP3 were negatively associated with overall survival, and the association for JUN was positive.

Conclusion: The current study identified key DEGs and their transcriptional regulatory networks involved in H. pylori-associated NAG, AG-IM and GC and found that patients with higher expressed FOXP3 or lower expressed JUN had shorter overall survival time. Our study provided new directions for inflammation-associated oncogenic transformation involved in H. pylori infection.

Keywords: DEGs; Gastric cancer; H. pylori; Inflammation; Regulatory network; Transcription factor.

Grants and funding

This work was supported by the National Natural Science Foundation of China (Award No. 81970501). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.