Identification of PTPN20 As an Innate Immunity-related Gene in Gastric Cancer with Helicobacter Pylori Infection

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jun 26

PMID 37359510

Authors

Lianjun Ma

Yang Liu

Yizhao Wang

Jiaxing Yang

Jordan Lu

Huijin Feng

Shujun Ye

Yanqing Liu

Affiliations

Soon will be listed here.

Abstract

Background: Gastric cancer (GC) is among the deadliest diseases with countless incidences and deaths each year. (Hp) is the primary type of microbe that colonizes the stomach. In recent years, increasing evidence has demonstrated that Hp infection is one of the main risk factors for GC. Elucidating the molecular mechanism of how Hp leads to GC will not only benefit the treatment of GC, but also boost the development of therapeutics for other gastric disorders caused by Hp infection. In this study, we aimed to identify innate immunity-related genes in GC and investigate their potentials as prognostic markers and therapeutic targets for Hp-related GC.

Methods: Firstly, we analyzed the differentially expressed innate immunity-related genes in GC samples from the TCGA database. Then prognostic correlation analysis was carried out to explore the prognostic value of these candidate genes. By combing transcriptome data, somatic mutation data, and clinical data, co-expression analysis, functional enrichment analysis, tumor mutational burden analysis, and immune infiltration analysis were performed to reveal the pathological relevance of the candidate gene. Finally, ceRNA network was constructed to identify the genes and pathways for the regulation of the candidate gene.

Results: We revealed that protein tyrosine phosphatase non-receptor type 20 (PTPN20) is a significant prognostic marker in Hp-related GC. Thus, PTPN20 levels have the potential to efficiently predict the survival of Hp-related GC patients. In addition, PTPN20 is associated with immune cell infiltration and tumor mutation burden in these GC patients. Moreover, we have also identified PTPN20-related genes, PTPN20 protein-protein interactions, and the PTPN20 ceRNA network.

Conclusion: Our data suggest that PTPN20 may have critical functions in Hp-related GC. Targeting PTPN20 may be a promising way to treat Hp-related GC.

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References

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

van Eekelen M, Runtuwene V, Masselink W, den Hertog J . Pair-wise regulation of convergence and extension cell movements by four phosphatases via RhoA. PLoS One. 2012; 7(4):e35913. PMC: 3335823. DOI: 10.1371/journal.pone.0035913. View

Dubois A, Boren T . Helicobacter pylori is invasive and it may be a facultative intracellular organism. Cell Microbiol. 2007; 9(5):1108-16. PMC: 1913845. DOI: 10.1111/j.1462-5822.2007.00921.x. View

Chen P, Lan J, Chen Y, Chen H, Chang S, Chung C . Anti-TROVE2 Antibody Determined by Immune-Related Array May Serve as a Predictive Marker for Adalimumab Immunogenicity and Effectiveness in RA. J Immunol Res. 2021; 2021:6656121. PMC: 7963899. DOI: 10.1155/2021/6656121. View

Fodero-Tavoletti M, Hardy M, Cornell B, Katsis F, Sadek C, Mitchell C . Protein tyrosine phosphatase hPTPN20a is targeted to sites of actin polymerization. Biochem J. 2005; 389(Pt 2):343-54. PMC: 1175111. DOI: 10.1042/BJ20041932. View

Sun F, Yu M, Yu J, Liu Z, Zhou X, Liu Y . miR-338-3p functions as a tumor suppressor in gastric cancer by targeting PTP1B. Cell Death Dis. 2018; 9(5):522. PMC: 5943282. DOI: 10.1038/s41419-018-0611-0. View

Liu Y, Zhang J, Du Z, Huang J, Cheng Y, Yi W . Comprehensive analysis of family expression and prognosis in acute myeloid leukemia. Front Genet. 2023; 13:1087938. PMC: 9868563. DOI: 10.3389/fgene.2022.1087938. View

Yang Y, Zhang J, Chen Y, Xu R, Zhao Q, Guo W . MUC4, MUC16, and TTN genes mutation correlated with prognosis, and predicted tumor mutation burden and immunotherapy efficacy in gastric cancer and pan-cancer. Clin Transl Med. 2020; 10(4):e155. PMC: 7443139. DOI: 10.1002/ctm2.155. View

Liu M, Yang R, Urrehman U, Ye C, Yan X, Cui S . MiR-19b suppresses PTPRG to promote breast tumorigenesis. Oncotarget. 2016; 7(39):64100-64108. PMC: 5325428. DOI: 10.18632/oncotarget.11799. View

10.

Long J, Jiang C, Liu B, Dai Q, Hua R, Chen C . Maintenance of stemness by miR-589-5p in hepatocellular carcinoma cells promotes chemoresistance via STAT3 signaling. Cancer Lett. 2017; 423:113-126. DOI: 10.1016/j.canlet.2017.11.031. View

11.

Liu Z, Sun F, Hong Y, Liu Y, Fen M, Yin K . MEG2 is regulated by miR-181a-5p and functions as a tumour suppressor gene to suppress the proliferation and migration of gastric cancer cells. Mol Cancer. 2017; 16(1):133. PMC: 5530520. DOI: 10.1186/s12943-017-0695-7. View

12.

Ferrero R . Innate immune recognition of the extracellular mucosal pathogen, Helicobacter pylori. Mol Immunol. 2005; 42(8):879-85. DOI: 10.1016/j.molimm.2004.12.001. View

13.

Suzuki H, Mori H . Helicobacter pylori: Helicobacter pylori gastritis--a novel distinct disease entity. Nat Rev Gastroenterol Hepatol. 2015; 12(10):556-7. DOI: 10.1038/nrgastro.2015.158. View

14.

Gambardella V, Castillo J, Tarazona N, Gimeno-Valiente F, Martinez-Ciarpaglini C, Cabeza-Segura M . The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target. Cancer Treat Rev. 2020; 86:102015. DOI: 10.1016/j.ctrv.2020.102015. View

15.

Hendriks W, Elson A, Harroch S, Pulido R, Stoker A, den Hertog J . Protein tyrosine phosphatases in health and disease. FEBS J. 2012; 280(2):708-30. DOI: 10.1111/febs.12000. View

16.

Paardekooper Overman J, den Hertog J . Zebrafish as a model to study PTPs during development. Methods. 2013; 65(2):247-53. DOI: 10.1016/j.ymeth.2013.08.018. View

17.

Polk D, Peek Jr R . Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010; 10(6):403-14. PMC: 2957472. DOI: 10.1038/nrc2857. View

18.

Ma L, Chen X, Li C, Cheng R, Gao Z, Meng X . miR-129-5p and -3p co-target WWP1 to suppress gastric cancer proliferation and migration. J Cell Biochem. 2018; 120(5):7527-7538. DOI: 10.1002/jcb.28027. View

19.

Marshall B, Warren J . Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984; 1(8390):1311-5. DOI: 10.1016/s0140-6736(84)91816-6. View

20.

Xu H, Miyajima M, Nakajima M, Ogino I, Kawamura K, Akiba C . Ptpn20 deletion in H-Tx rats enhances phosphorylation of the NKCC1 cotransporter in the choroid plexus: an evidence of genetic risk for hydrocephalus in an experimental study. Fluids Barriers CNS. 2022; 19(1):39. PMC: 9164390. DOI: 10.1186/s12987-022-00341-z. View