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Article | Open Access

Identification of aging-related genes in Helicobacter pylori infection

Honghao Li, Yuanyuan Deng, Honglie Zeng, Shaowei Cai, Ming Xu, Hongli Zhao( )
Department of Internal Medicine II, Minhang Campus, Guangdong Second Provincial General Hospital, Guangzhou 510317, China
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Abstract

Background

Helicobacter pylori (HP) infection is common worldwide, leading to many systemic diseases. The reasons for aging have been explored, but there is no unified conclusion. The aim of this study was to explore aging-related genes involved in HP infection.

Results

A total of 70 aging-related differentially expressed genes (DEGs) were identified between HP infection and control groups, including 64 upregulated genes and 6 downregulated genes. Functional enrichment analysis revealed that multiple signaling pathways are closely linked to HP infection. In addition, the cytoHubba plugin identified 10 important hub genes, namely, ITGB2, PTPRC, HCLS1, LAPTM5, CD53, LYN, HLA-DRA, HLA-DPA1, HLA-DQB1, and CXCL8. Additionally, the correlation analysis of immune cell fractions revealed that immune infiltration plays an important role in HP infection. The nomogram containing CD53, ITGB2, and CXCL8 confirmed the favorable prediction ability of HP infection.

Conclusion

Ten aging-related hub genes involved in HP infection were identified. This study revealed an association between aging and HP infection, and they may have a causal relationship.

Methods

Microarray data for HP infection were obtained from the Gene Expression Omnibus (GEO) database. Aging-related genes were obtained from the Molecular Signature Database (https://www.gsea-msigdb.org). Differential gene expression analysis was analysed using R software and the limma package to find DEGs. In addition, functional enrichment analysis of DEGs by using GO and KEGG and construction of protein‒protein interactions (PPIs) and hub genes were determined by using the STRING database and Cytoscape software. Additionally, immune infiltration and difference analysis between HP infection and control groups were performed with R software. A nomogram was constructed to predict the risk of infection with HP by using some hub genes that were strongly correlated with neutrophils.

Keywords

aginghub genesHelicobacter pylori (HP)immune infiltration

References

[1]

Marshall, B., Warren, J. R. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. The Lancet, 1984, 323: 1311–1315. https://doi.org/10.1016/S0140-6736(84)91816-6
Crossref Google Scholar
[2]

Gobert, A. P., Wilson, K. T. Induction and regulation of the innate immune response in Helicobacter pylori infection. Cellular and Molecular Gastroenterology and Hepatology, 2022, 13: 1347–1363. https://doi.org/10.1016/j.jcmgh.2022.01.022
Crossref Google Scholar
[3]

Xu, W. T., Xu, L. M., Xu, C. F. Relationship between Helicobacter pylori infection and gastrointestinal microecology. Frontiers in Cellular and Infection Microbiology, 2022, 12: 938608. https://doi.org/10.3389/fcimb.2022.938608
Crossref Google Scholar
[4]
Ito, N., Tsujimoto, H., Ueno, H., Xie, Q., Shinomiya, N. Helicobacter pylori-mediated immunity and signaling transduction in gastric cancer. Journal of Clinical Medicine, 2020, 9(11): 3699. https://doi.org/10.3390/jcm9113699
Crossref
[5]

Mentis, A. F A., Boziki, M., Grigoriadis, N., Papavassiliou, A. G. Helicobacter pylori infection and gastric cancer biology: Tempering a double-edged sword. Cellular and Molecular Life Sciences, 2019, 76: 2477–2486. https://doi.org/10.1007/s00018-019-03044-1
Crossref Google Scholar
[6]
Santos, M. L. C., Brito, B. B. D., Silva, F. A. F. D., Sampaio, M. M., Marques, H. S., Silva, N. O. E., de Magalhães Queiroz, D. M., Melo, F. F. D. Helicobacter pylori infection: Beyond gastric manifestations. World Journal of Gastroenterology, 2020, 26(28): 4076–4093. https://doi.org/10.3748/wjg.v26.i28.4076
Crossref
[7]
Mladenova, I. Clinical relevance of Helicobacter pylori infection. Journal of Clinical Medicine, 2021, 10(16): 3473. https://doi.org/10.3390/jcm10163473
Crossref
[8]
de Brito, B. B., da Silva, F. A. F., Soares, A. S., Pereira, V. A., Santos, M. L. C., Sampaio, M. M., Neves, P. H. M., de Melo, F. F. Pathogenesis and clinical management of Helicobacter pylori gastric infection. World Journal of Gastroenterology, 2019, 25(37): 5578–5589. https://doi.org/10.3748/wjg.v25.i37.5578
Crossref
[9]

Yunhao, Li, MMed,. Global prevalence of Helicobacter pylori infection between 1980 and 2022: A systematic review and meta-analysis. The Lancet Gastroenterology & Hepatology, 2023, 8: 553–564. https://doi.org/10.1016/S2468-1253(23)00070-5
Crossref Google Scholar
[10]

Ikeda, H., Togashi, Y. Aging, cancer, and antitumor immunity. International Journal of Clinical Oncology, 2022, 27: 316–322. https://doi.org/10.1007/s10147-021-01913-z
Crossref Google Scholar
[11]

Hou, Y. J., Dan, X. L., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., Bohr, V. A. Ageing as a risk factor for neurodegenerative disease. Nature Reviews Neurology, 2019, 15: 565–581. https://doi.org/10.1038/s41582-019-0244-7
Crossref Google Scholar
[12]

López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., Kroemer, G. Hallmarks of aging: An expanding universe. Cell, 2023, 186: 243–278. https://doi.org/10.1016/j.cell.2022.11.001
Crossref Google Scholar
[13]

Giannoula, Y., Kroemer, G., Pietrocola, F. Cellular senescence and the host immune system in aging and age-related disorders. Biomedical Journal, 2023, 46: 100581. https://doi.org/10.1016/j.bj.2023.02.001
Crossref Google Scholar
[14]

Xiao, X., Yeoh, B. S., Vijay-Kumar, M. Lipocalin 2: An emerging player in iron homeostasis and inflammation. Annual Review of Nutrition, 2017, 37: 103–130. https://doi.org/10.1146/annurev-nutr-071816-064559
Crossref Google Scholar
[15]

Xu, W. X., Zhang, J., Hua, Y. T., Yang, S. J., Wang, D. D., Tang, J. H. An integrative pan-cancer analysis revealing LCN2 as an oncogenic immune protein in tumor microenvironment. Frontiers in Oncology, 2020, 10: 605097. https://doi.org/10.3389/fonc.2020.605097
Crossref Google Scholar
[16]

Qiu, X. X., Chen, C., Chen, X. L. Lipocalin 2 deficiency restrains aging-related reshaping of gut microbiota structure and metabolism. Biomolecules, 2021, 11: 1286. https://doi.org/10.3390/biom11091286
Crossref Google Scholar
[17]

Iino, C., Shimoyama, T. Impact of Helicobacter pylori infection on gut microbiota. World Journal of Gastroenterology, 2021, 27: 6224–6230. https://doi.org/10.3748/wjg.v27.i37.6224
Crossref Google Scholar
[18]

Martin-Nuñez, G. M., Cornejo-Pareja, I., Clemente-Postigo, M., Tinahones, F. J. Gut microbiota: The missing link between Helicobacter pylori infection and metabolic disorders. Frontiers in Endocrinology, 2021, 12: 639856. https://doi.org/10.3389/fendo.2021.639856
Crossref Google Scholar
[19]
Tao, Z. H., Han, J. X., Fang, J. Y. Helicobacter pylori infection and eradication: Exploring their impacts on the gastrointestinal microbiota. Helicobacter, 2020, 25(6): e12754. https://doi.org/10.1111/hel.12754
Crossref
[20]

Bungau, S. G., Behl, T., Singh, A., Sehgal, A., Singh, S., Chigurupati, S., Vijayabalan, S., Das, S., Palanimuthu, V. R. Targeting probiotics in rheumatoid arthritis. Nutrients, 2021, 13: 3376. https://doi.org/10.3390/nu13103376
Crossref Google Scholar
[21]

Xu, Q., Ni, J. J., Han, B. X., Yan, S. S., Wei, X. T., Feng, G. J., Zhang, H., Zhang, L., Li, B., Pei, Y. F. Causal relationship between gut microbiota and autoimmune diseases: A two-sample Mendelian randomization study. Frontiers in Immunology, 2021, 12: 746998. https://doi.org/10.3389/fimmu.2021.746998
Crossref Google Scholar
[22]

Griffith, J. W., Sokol, C. L., Luster, A. D. Chemokines and chemokine receptors: Positioning cells for host defense and immunity. Annual Review of Immunology, 2014, 32: 659–702. https://doi.org/10.1146/annurev-immunol-032713-120145
Crossref Google Scholar
[23]

Zou, Q., Lei, X., Xu, A. J., Li, Z. Q., He, Q. L., Huang, X. J., Xu, G. X., Tian, F. Q., Ding, Y. L., Zhu, W. Chemokines in progression, chemoresistance, diagnosis, and prognosis of colorectal cancer. Frontiers in Immunology, 2022, 13: 724139. https://doi.org/10.3389/fimmu.2022.724139
Crossref Google Scholar
[24]

C, V., Grant,. Manipulations of the gut microbiome alter chemotherapy-induced inflammation and behavioral side effects in female mice. Brain, Behavior, and Immunity, 2021, 95: 401–412. https://doi.org/10.1016/j.bbi.2021.04.014
Crossref Google Scholar
[25]

Aho, V. T. E., Houser, M. C., Pereira, P. A. B., Chang, J. J., Rudi, K., Paulin, L., Hertzberg, V., Auvinen, P., Tansey, M. G., Scheperjans, F. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease. Molecular Neurodegeneration, 2021, 16: 6. https://doi.org/10.1186/s13024-021-00427-6
Crossref Google Scholar
[26]

Kim, H. N., Kim, M. J., Jacobs, J. P., Yang, H. J. Altered gastric microbiota and inflammatory cytokine responses in patients with Helicobacter pylori-negative gastric cancer. Nutrients, 2022, 14: 4981. https://doi.org/10.3390/nu14234981
Crossref Google Scholar
[27]

Liu, X. Z., Li, M., Han, Q., Zuo, Z. Y., Wang, Q., Su, D. P., Fan, M. M., Chen, T. Exploring a shared genetic signature and immune infiltration between spontaneous intracerebral hemorrhage and Helicobacter pylori infection. Microbial Pathogenesis, 2023, 178: 106067. https://doi.org/10.1016/j.micpath.2023.106067
Crossref Google Scholar
[28]

Korbecki, J., Szatkowska, I., Kupnicka, P., Żwierełło, W., Barczak, K., Poziomkowska-Gęsicka, I., Wójcik, J., Chlubek, D., Baranowska-Bosiacka, I. The importance of CXCL1 in the physiological state and in noncancer diseases of the oral cavity and abdominal organs. International Journal of Molecular Sciences, 2022, 23: 7151. https://doi.org/10.3390/ijms23137151
Crossref Google Scholar
[29]

Yi-yun, Tan,. The improvement of nonalcoholic steatohepatitis by Poria cocos polysaccharides associated with gut microbiota and NF-κB/CCL3/CCR1 axis. Phytomedicine, 2022, 103: 154208. https://doi.org/10.1016/j.phymed.2022.154208
Crossref Google Scholar
[30]

Zhai, L. L., Yang, W. M., Li, D. R., Zhou, W., Cui, M., Yao, P. Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome. Journal of Pharmacy and Pharmaceutical Science, 2023, 26: 11225. https://doi.org/10.3389/jpps.2023.11225
Crossref Google Scholar
[31]
Maubach, G., Vieth, M., Boccellato, F., Naumann, M. Helicobacter pylori-induced NF-κB: Trailblazer for gastric pathophysiology. Trends in Molecular Medicine, 2022, 28(3): 210–222. https://doi.org/10.1016/j.molmed.2021.12.005
Crossref
[32]
Hannah, B., Taylor, . MS-based HLA-II peptidomics combined with multiomics will aid the development of future immunotherapies. Molecular & Cellular Proteomics, 2021, 20: 100116. https://doi.org/10.1016/j.mcpro.2021.100116
Crossref
[33]

Shao, X. M., Bhattacharya, R., Huang, J., Sivakumar, I. K. A., Tokheim, C., Zheng, L., Hirsch, D., Kaminow, B., Omdahl, A., Bonsack, M. et al. High-throughput prediction of MHC class I and II neoantigens with MHCnuggets. Cancer Immunology Research, 2020, 8: 396–408. https://doi.org/10.1158/2326-6066.cir-19-0464
Crossref Google Scholar
[34]

Rappazzo, C. G., Huisman, B. D., Birnbaum, M. E. Repertoire-scale determination of class II MHC peptide binding via yeast display improves antigen prediction. Nature Communications, 2020, 11: 4414. https://doi.org/10.1038/s41467-020-18204-2
Crossref Google Scholar
[35]
Codolo, G., Toffoletto, M., Chemello, F., Coletta, S., Soler Teixidor, G., Battaggia, G., Munari, G., Fassan, M., Cagnin, S., de Bernard, M. Helicobacter pylori dampens HLA-II expression on macrophages via the up-regulation of miRNAs targeting CIITA. Frontiers in Immunology, 2020, 10: 2923. https://doi.org/10.3389/fimmu.2019.02923
Crossref
[36]

Zhang, X. X., Dong, Y. C., Zhao, M. X., Ding, L., Yang, X. H., Jing, Y., Song, Y. X., Chen, S., Hu, Q. G., Ni, Y. H. ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system. Theranostics, 2020, 10: 12044–12059. https://doi.org/10.7150/thno.47901
Crossref Google Scholar
[37]

Liu, H., Dai, X. M., Cao, X. L., Yan, H., Ji, X. Y., Zhang, H. T., Shen, S. Y., Si, Y., Zhang, H. L., Chen, J. F. et al. PRDM 4 mediatesYAP-induced cell invasion by activating leukocyte-specific integrin β2 expression. EMBO Reports, 2018, 19: e45180. https://doi.org/10.15252/embr.201745180
Crossref Google Scholar
[38]

Blight, B. J., Gill, A. S., Sumsion, J. S., Pollard, C. E., Ashby, S., Oakley, G. M., Alt, J. A., Pulsipher, A. Cell adhesion molecules are upregulated and may drive inflammation in chronic rhinosinusitis with nasal polyposis. Journal of Asthma and Allergy, 2021, 14: 585–593. https://doi.org/10.2147/jaa.s307197
Crossref Google Scholar
[39]

Zhu, Y., Sun, X. W., Tan, S. L., Lou, C. Y., Zhou, J. Y., Zhang, S. Y., Li, Z. P., Lin, H., Zhang, W. T. M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps. Frontiers in Immunology, 2022, 13: 1047930. https://doi.org/10.3389/fimmu.2022.1047930
Crossref Google Scholar
[40]

Latour, Y. L., Sierra, J. C., Finley, J. L., Asim, M., Barry, D. P., Allaman, M. M., Smith, T. M., McNamara, K. M., Luis, P. B., Schneider, C. et al. Cystathionine γ-lyase exacerbates Helicobacter pylori immunopathogenesis by promoting macrophage metabolic remodeling and activation. JCI Insight, 2022, 7: e155338. https://doi.org/10.1172/jci.insight.155338
Crossref Google Scholar
[41]

Hubbard, S. R., Till, J. H. Protein tyrosine kinase structure and function. Annual Review of Biochemistry, 2000, 69: 373–398. https://doi.org/10.1146/annurev.biochem.69.1.373
Crossref Google Scholar
[42]
Liu, Z. C., Li, J. C., Hu, X. S., Xu, H. W. Helicobacter pylori-induced protein tyrosine phosphatase receptor type C as a prognostic biomarker for gastric cancer. Journal of Gastrointestinal Oncology, 2021, 12(3): 1058–1073. https://doi.org/10.21037/jgo-21-305
Crossref
[43]

Adra, C. N., Zhu, S. C., Ko, J.-L., Guillemot, J-C., Cuervo, A. M., Kobayashi, H., Horiuchi, T., Lelias, J.-M., Rowley, J. D., Lim, B. LAPTM5: A novel lysosomal-associated multispanning membrane protein preferentially expressed in hematopoietic cells. Genomics, 1996, 35: 328–337. https://doi.org/10.1006/geno.1996.0364
Crossref Google Scholar
[44]
Reyes, V. E., Peniche, A. G. Helicobacter pylori deregulates T and B cell signaling to trigger immune evasion. Current Topics in Microbiology and Immunology. Cham: Springer International Publishing, 2019: 229–265. https://doi.org/10.1007/978-3-030-15138-6_10
Crossref
[45]

Brian, B. F., Freedman, T. S. The src-family kinase lyn in immunoreceptor signaling. Endocrinology, 2021, 162: 1–13. https://doi.org/10.1210/endocr/bqab152
Crossref Google Scholar
[46]

Yamanashi, Y., Fukuda, T., Nishizumi, H., Inazu, T., Higashi, K. I., Kitamura, D., Ishida, T., Yamamura, H., Watanabe, T., Yamamoto, T. Role of tyrosine phosphorylation of HS1 in B cell antigen receptor-mediated apoptosis. The Journal of Experimental Medicine, 1997, 185: 1387–1392. https://doi.org/10.1084/jem.185.7.1387
Crossref Google Scholar
[47]
Sampietro, M., Zamai, M., Díaz Torres, A., Labrador Cantarero, V., Barbaglio, F., Scarfò, L., Scielzo, C., Caiolfa, V. R. 3D-STED super-resolution microscopy reveals distinct nanoscale organization of the hematopoietic cell-specific lyn substrate-1 (HS1) in normal and leukemic B cells. Frontiers in Cell and Developmental Biology, 2021, 9: 655773. https://doi.org/10.3389/fcell.2021.655773
Crossref
[48]

Dunlock, V. E. Tetraspanin CD53: An overlooked regulator of immune cell function. Medical Microbiology and Immunology, 2020, 209: 545–552. https://doi.org/10.1007/s00430-020-00677-z
Crossref Google Scholar
[49]

Poto, R., Cristinziano, L., Modestino, L., de Paulis, A., Marone, G., Loffredo, S., Galdiero, M. R., Varricchi, G. Neutrophil extracellular traps, angiogenesis and cancer. Biomedicines, 2022, 10: 431. https://doi.org/10.3390/biomedicines10020431
Crossref Google Scholar
[50]

Prichard, A., Khuu, L., Whitmore, L. C., Irimia, D., Allen, L. A H. Helicobacter pylori-infected human neutrophils exhibit impaired chemotaxis and a uropod retraction defect. Frontiers in Immunology, 2022, 13: 1038349. https://doi.org/10.3389/fimmu.2022.1038349
Crossref Google Scholar
Aging Research
Volume 1 Issue 1,
September 2023
Article number: 9340013
DOI: 10.26599/AGR.2023.9340013
Cite this article:
Li H, Deng Y, Zeng H, et al. Identification of aging-related genes in Helicobacter pylori infection. Aging Research, 2023, 1(1): 9340013. https://doi.org/10.26599/AGR.2023.9340013

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Received: 21 August 2023
Revised: 30 August 2023
Accepted: 31 August 2023
Published: 23 October 2023
© The Author(s) 2023. Aging Research published by Tsinghua University Press.

The articles published in this open access journal are distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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