Transcriptomic analysis reveals the promotion of lymph node metastasis by <em>Helicobacter pylori</em> infection via upregulating chemokine (C-X-C motif) receptor 2 expression in gastric carcinoma

Lang Zha; Xiong Guo; Xiaolong Liang; Yuedong Chen; Deyong Gan; Wenwen Li; Ziwei Wang; Hongyu Zhang

doi:10.1016/j.gendis.2022.10.027

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Transcriptomic analysis reveals the promotion of lymph node metastasis by Helicobacter pylori infection via upregulating chemokine (C-X-C motif) receptor 2 expression in gastric carcinoma

Full-length article | 更新时间：2024-02-04

- Transcriptomic analysis reveals the promotion of lymph node metastasis by Helicobacter pylori infection via upregulating chemokine (C-X-C motif) receptor 2 expression in gastric carcinoma
- Genes & Diseases Vol. 1, Issue 6, Pages: 2614-2621(2023)
- 作者机构：
  
  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University,Chongqing,China,400010
  2. Department of Gastrointestinal Surgery, The Tongliang Hospital of the First Affiliated Hospital of Chongqing Medical University,Chongqing,China,400010
  3. Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University,Chongqing,China,400016
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2022.10.027
  CLC：
- Published：2023，
  
  Published Online：1 November 2023，
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Lang Zha, Xiong Guo, Xiaolong Liang, et al. Transcriptomic analysis reveals the promotion of lymph node metastasis by Helicobacter pylori infection via upregulating chemokine (C-X-C motif) receptor 2 expression in gastric carcinoma. [J]. Genes & Diseases 1(6):2614-2621(2023)
DOI：

Lang Zha, Xiong Guo, Xiaolong Liang, et al. Transcriptomic analysis reveals the promotion of lymph node metastasis by Helicobacter pylori infection via upregulating chemokine (C-X-C motif) receptor 2 expression in gastric carcinoma. [J]. Genes & Diseases 1(6):2614-2621(2023) DOI： 10.1016/j.gendis.2022.10.027.

摘要

Abstract

Gastric carcinoma (GC) progression is mainly caused by local aggression and lymph node metastasis. However

some patients with early T-stage disease have lymph node metastasis

whereas some patients with late T-stage disease do not have lymph node metastasis

which indicates that invasion and metastasis are not always sequential in some GC patients. In the present study

the data of 101 GC cases were acquired from TCGA and divided into T-late-N-negative and T-early-N-positive groups according to pathological stages. A total of 338 genes were identified as differential genes between the T-late-N-negative and T-early-N-positive groups. GSEA showed that epithelial cell signaling in the

Helicobacter pylori

(

) infection pathway was enriched in the T-early-N-positive group. MB staining indicated that the

infection rate was 63% (39/62) in N-positive patients compared to 42% (16/38) in N-negative patients. To investigate the potential mechanism

we focused on the gene chemokine (C-X-C motif) receptor 2 (CXCR2)

which was not only clustered in the gene set of epithelial cells signaling in the

infection pathway but also significantly upregulated in T-early-N-positive GC by the analysis of the different genes based on the TCGA dataset. A meta-analysis showed that CXCR2 expression was positively correlated with N-stage but not with T-stage in GC. This study indicated that invasion and metastasis could be independent processes driven by different molecular mechanisms in some GC patients.

infection was a potential factor that promoted lymph node metastasis by upregulating CXCR2 expression.

关键词

Keywords

CXCR2Gastric carcinomaHelicobacter pyloriInvasionLymph node metastasis

references

1 H. Sung, J. Ferlay, R.L. Siegel, et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA A Cancer J Clin, 71 (3) (2021), pp. 209-249

2 A.C. Ford, Y. Yuan, P. MoayyediHelicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis Gut, 69 (12) (2020), pp. 2113-2121

3 F. Imazeki, M. Omata, H. Nose, et al.p53 gene mutations in gastric and esophageal cancers Gastroenterology, 103 (3) (1992), pp. 892-896

4 M. Tanner, M Hollmén, TT Junttila, et al.Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIα gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab Ann Oncol, 16 (2) (2005), pp. 273-278

5 F. Graziano, B. Humar, P. GuilfordThe role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice Ann Oncol, 14 (12) (2003), pp. 1705-1713

6 H. Allgayer, R. Babic, K.U. Gruetzner, et al.C-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems J Clin Oncol, 18 (11) (2000), pp. 2201-2209

7 M. Canale, A. Casadei-Gardini, P. Ulivi, et al.Epigenetic mechanisms in gastric cancer: potential new therapeutic opportunities Int J Mol Sci, 21 (15) (2020), p. 5500

8 D. Hanahan, R.A. WeinbergThe hallmarks of cancer Cell, 100 (1) (2000), pp. 57-70

9 D. Hanahan, R.A. WeinbergHallmarks of cancer: the next generation Cell, 144 (5) (2011), pp. 646-674

10 R.A. Busuttil, J. George, C.M. House, et al.SFRP4 drives invasion in gastric cancer and is an early predictor of recurrence Gastric Cancer, 24 (3) (2021), pp. 589-601

11 K. Yang, L. Lu, H. Liu, et al.A comprehensive update on early gastric cancer: defining terms, etiology, and alarming risk factors Expet Rev Gastroenterol Hepatol, 15 (3) (2021), pp. 255-273

12 A. Subramanian, P. Tamayo, V.K. Mootha, et al.Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles Proc Natl Acad Sci U S A, 102 (43) (2005), pp. 15545-15550

13 V.K. Mootha, C.M. Lindgren, K.F. Eriksson, et al.PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes Nat Genet, 34 (3) (2003), pp. 267-273

14 A. Liberzon, C. Birger, H. Thorvaldsdóttir, et al.The Molecular Signatures Database (MSigDB) hallmark gene set collection Cell Syst, 1 (6) (2015), pp. 417-425

15 X. Chu, J. Xu, L. NiuComparative study of modified silver nitrate staining for the detection of Helicobacter pylori Appl Immunohistochem Mol Morphol, 30 (5) (2022), pp. 340-344

16 Z. Xiang, Z.J. Zhou, G.K. Xia, et al.A positive crosstalk between CXCR4 and CXCR2 promotes gastric cancer metastasis Oncogene, 36 (36) (2017), pp. 5122-5133

17 Z. Wang, H. Liu, Z. Shen, et al.The prognostic value of CXC-chemokine receptor 2 (CXCR2) in gastric cancer patients BMC Cancer, 15 (2015), p. 766

18 Z. Li, Y. Wang, S. Dong, et al.Association of CXCR1 and 2 expressions with gastric cancer metastasis in ex vivo and tumor cell invasion in vitro. Cytokine, 69 (1) (2014), pp. 6-13

19 H. Kasashima, M. Yashiro, H. Nakamae, et al.Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma PLoS One, 12 (6) (2017), Article e0178635

20 S.B. Yang, F. Han, J.H. Wu, et al.Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression Oncol Lett, 12 (2) (2016), pp. 1477-1484

21 J. Xu, C. Zhang, Y. He, et al.Lymphatic endothelial cell-secreted CXCL1 stimulates lymphangiogenesis and metastasis of gastric cancer Int J Cancer, 130 (4) (2012), pp. 787-797

22 I. Pastushenko, C. BlanpainEMT transition states during tumor progression and metastasis Trends Cell Biol, 29 (3) (2019), pp. 212-226

23 T. Brabletz, R. Kalluri, M.A. Nieto, et al.EMT in cancer Nat Rev Cancer, 18 (2) (2018), pp. 128-134

24 J. Wang, Z. Zhang, R. Li, et al.ADAM12 induces EMT and promotes cell migration, invasion and proliferation in pituitary adenomas via EGFR/ERK signaling pathway Biomed Pharmacother, 97 (2018), pp. 1066-1077

25 L. Zha, J. Zhang, W. Tang, et al.HMGA2 elicits EMT by activating the Wnt/β-catenin pathway in gastric cancer Dig Dis Sci, 58 (3) (2013), pp. 724-733

26 X. Feng, X.M.Y. ShiCorrelations of recurrence of gastric cancer in patients after radical surgery with serum gastrointestinal hormones, vascular endothelial growth factors and serum anti-Helicobacter pylori IgG antibody J BUON, 25 (3) (2020), pp. 1476-1481

27 F. Bäckhed, E. Torstensson, D. Seguin, et al.Helicobacter pylori infection induces interleukin-8 receptor expression in the human gastric epithelium Infect Immun, 71 (6) (2003), pp. 3357-3360

28 S.K. Ahuja, T. Ozçelik, A. Milatovitch, et al.Molecular evolution of the human interleukin-8 receptor gene cluster Nat Genet, 2 (1) (1992), pp. 31-36

29 H. Xu, F. Lin, Z. Wang, et al.CXCR2 promotes breast cancer metastasis and chemoresistance via suppression of AKT1 and activation of COX2 Cancer Lett, 412 (2018), pp. 69-80

30 L. Han, B. Jiang, H. Wu, et al.High expression of CXCR2 is associated with tumorigenesis, progression, and prognosis of laryngeal squamous cell carcinoma Med Oncol, 29 (4) (2012), pp. 2466-2472

31 P. Sui, P. Hu, T. Zhang, et al.High expression of CXCR-2 correlates with lymph node metastasis and predicts unfavorable prognosis in resected esophageal carcinoma Med Oncol, 31 (2) (2014), p. 809

32 J. Zhao, B. Ou, H. Feng, et al.Overexpression of CXCR2 predicts poor prognosis in patients with colorectal cancer Oncotarget, 8 (17) (2017), pp. 28442-28454

33 G. Yang, D.G. Rosen, G. Liu, et al.CXCR2 promotes ovarian cancer growth through dysregulated cell cycle, diminished apoptosis, and enhanced angiogenesis Clin Cancer Res, 16 (15) (2010), pp. 3875-3886

34 X. Wu, J. Xia, Z. Wang, et al.Feiyanning downregulating CXCLs/CXCR2 axis to suppress TANs infiltration in the prevention of lung cancer metastasis J Ethnopharmacol, 295 (2022), Article 115277

35 H. Sueoka, T. Hirano, Y. Uda, et al.Blockage of CXCR2 suppresses tumor growth of intrahepatic cholangiocellular carcinoma Surgery, 155 (4) (2014), pp. 640-649

36 C.W. Steele, S.A. Karim, J.D.G. Leach, et al.CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma Cancer Cell, 29 (6) (2016), pp. 832-845

37 M. Sano, H. Ijichi, R. Takahashi, et al.Blocking CXCLs-CXCR2 axis in tumor-stromal interactions contributes to survival in a mouse model of pancreatic ductal adenocarcinoma through reduced cell invasion/migration and a shift of immune-inflammatory microenvironment Oncogenesis, 8 (2) (2019), p. 8

38 F. Munari, S. Lonardi, M.A. Cassatella, et al.Tumor-associated macrophages as major source of APRIL in gastric MALT lymphoma Blood, 117 (24) (2011), pp. 6612-6616

39 K. Sugizaki, A. Tari, Y. Kitadai, et al.Anti-Helicobacter pylori therapy in localized gastric mucosa-associated lymphoid tissue lymphoma: a prospective, nationwide, multicenter study in Japan Helicobacter, 23 (2) (2018), Article e12474

40 S. Devi, S.A. Ansari, J. Vadivelu, et al.Helicobacter pylori antigen HP0986 (TieA) interacts with cultured gastric epithelial cells and induces IL8 secretion via NF-κB mediated pathway Helicobacter, 19 (1) (2014), pp. 26-36

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Transcriptomic analysis reveals the promotion of lymph node metastasis by Helicobacter pylori infection via upregulating chemokine (C-X-C motif) receptor 2 expression in gastric carcinoma

DOI：10.1016/j.gendis.2022.10.027

摘要

Abstract

关键词

Keywords

references