Vol 60, No 1 (2022)
Original paper
Published online: 2022-01-17

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Overexpression of IL-8 and Wnt2 is associated with prognosis of gastric cancer

Li Lin1, Linjing Li2, Gui Ma3, Yaqiong Kang3, Xingdong Wang4, Jianxin He5
Pubmed: 35037695
Folia Histochem Cytobiol 2022;60(1):66-73.

Abstract

Introduction. This study is to detect the expression of inflammatory factor or neutrophil-activating factor IL-8 and Wnt2 in gastric cancer (GC) and investigate the involvement of IL-8 and Wnt2 expressions in the clinicopathological indexes and prognosis.

Material and methods. We detected the expression of IL-8 and Wnt2 in 100 GC tissues and 40 normal gastric mucosae using immunohistochemistry. The relationships between the IL-8 and Wnt2 expression and the clinicopathological characteristics were explored. The relationship between IL-8 expression, Wnt2 expression, and prognosis of GC was analyzed by survival curve and survival regression.

Results. The expression of IL-8 and Wnt2 in GC tissue was 64% and 75% respectively, which was significantly higher than that in adjacent normal gastric mucosa tissues, moreover, expressions of IL-8 and Wnt2 were positively correlated. The positive rate of IL-8 and Wnt2 expressions were correlated with lymph node metastasis and TNM staging (P < 0.01, and Wnt2 was also correlated with infiltration depth (P = 0.021), but there was no difference with age, sex, and differentiation (P > 0.05). The 3-year survival analysis showed that the survival rates of IL-8- and Wnt2-positive patients were 20% and 24%, respectively, which were significantly lower than those of negative patients. Cox regression analysis showed that IL-8 and Wnt2 may be independent factors affecting the prognosis of GC.

Conclusions. Our data demonstrated that the overexpression of IL-8 and Wnt2 could be isolated prognostic
factors in patients with GC and, possibly, may present new targets for the treatment of GC.

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References

  1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394–424.
  2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2): 115–132.
  3. Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer. 2007; 121(11): 2373–2380.
  4. Molaei F, Forghanifard MM, Fahim Y, et al. Molecular Signaling in Tumorigenesis of Gastric Cancer. Iran Biomed J. 2018; 22(4): 217–230.
  5. David JM, Dominguez C, Hamilton DH, et al. The IL-8/IL-8R Axis: A Double Agent in Tumor Immune Resistance. Vaccines (Basel). 2016; 4(3).
  6. Visciano C, Liotti F, Prevete N, et al. Mast cells induce epithelial-to-mesenchymal transition and stem cell features in human thyroid cancer cells through an IL-8-Akt-Slug pathway. Oncogene. 2015; 34(40): 5175–5186.
  7. Palena C, Hamilton DH, Fernando RI. Influence of IL-8 on the epithelial-mesenchymal transition and the tumor microenvironment. Future Oncol. 2012; 8(6): 713–722.
  8. Ha H, Debnath B, Neamati N. Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases. Theranostics. 2017; 7(6): 1543–1588.
  9. Bosco MC, Gusella GL, Espinoza-Delgado I, et al. Interferon-gamma upregulates interleukin-8 gene expression in human monocytic cells by a posttranscriptional mechanism. Blood. 1994; 83(2): 537–542.
  10. Mukaida N, Murayama T. Molecular mechanism of interleukin-8 gene expression. Rinsho Byori. 1998; 46(8): 821–828.
  11. Waugh DJJ, Wilson C. The interleukin-8 pathway in cancer. Clin Cancer Res. 2008; 14(21): 6735–6741.
  12. Burz C, Bojan A, Balacescu L, et al. Interleukin 8 as predictive factor for response to chemotherapy in colorectal cancer patients. Acta Clin Belg. 2019; 76(2): 113–118.
  13. Ning Y, Manegold PC, Hong YK, et al. Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models. Int J Cancer. 2011; 128(9): 2038–2049.
  14. Liu Y, Xu Y, Wang Y, et al. Associations between interleukin gene polymorphisms and the risk of gastric cancer: A meta-analysis. Clin Exp Pharmacol Physiol. 2018; 45(12): 1236–1244.
  15. Huang S, Mills L, Mian B, et al. Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma. Am J Pathol. 2002; 161(1): 125–134.
  16. Inoue K, Slaton JW, Kim SJ, et al. Interleukin 8 expression regulates tumorigenicity and metastasis in human bladder cancer. Cancer Res. 2000; 60(8): 2290–2299.
  17. Al-Khalaf HH, Al-Harbi B, Al-Sayed A, et al. Interleukin-8 Activates Breast Cancer-Associated Adipocytes and Promotes Their Angiogenesis- and Tumorigenesis-Promoting Effects. Mol Cell Biol. 2019; 39(2).
  18. Inoue K, Slaton JW, Eve BY, et al. Interleukin 8 expression regulates tumorigenicity and metastases in androgen-independent prostate cancer. Clin Cancer Res. 2000; 6(5): 2104–2119.
  19. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell. 2012; 149: 1192–1205.
  20. Chiurillo MA. Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review. World J Exp Med. 2015; 5(2): 84–102.
  21. Katoh M, Hirai M, Sugimura T, et al. Cloning, expression and chromosomal localization of Wnt-13, a novel member of the Wnt gene family. Oncogene. 1996; 13(4): 873–876.
  22. Katoh M. WNT2B: comparative integromics and clinical applications (Review). Int J Mol Med. 2005; 16(6): 1103–1108.
  23. Zhang Z, Wang J, Dong X. Wnt2 contributes to the progression of gastric cancer by promoting cell migration and invasion. Oncol Lett. 2018; 16(3): 2857–2864.
  24. Mao J, Fan S, Ma W, et al. Roles of Wnt/β-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell Death Dis. 2014; 5: e1039.
  25. Katoh M. WNT2 and human gastrointestinal cancer (Review). Int J Mol Med. 2003.
  26. Lin Li, Wei H, Yi J, et al. Chronic CagA-positive Helicobacter pylori infection with MNNG stimulation synergistically induces mesenchymal and cancer stem cell-like properties in gastric mucosal epithelial cells. J Cell Biochem. 2019; 120(10): 17635–17649.
  27. Chen Xi, Yu X, Shen E. Overexpression of CDKN2B is involved in poor gastric cancer prognosis. J Cell Biochem. 2019; 120(12): 19825–19831.
  28. Peveri P, Walz A, Dewald B, et al. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988; 167(5): 1547–1559.
  29. Larsen CG, Anderson AO, Appella E, et al. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science. 1989; 243(4897): 1464–1466.
  30. Auer M, Kallen J, Schleischitz S, et al. Crystallization and preliminary X-ray crystallographic study of interleukin-8. FEBS Lett. 1990; 265(1-2): 30–32.
  31. Alfaro C, Sanmamed MF, Rodríguez-Ruiz ME, et al. Interleukin-8 in cancer pathogenesis, treatment and follow-up. Cancer Treat Rev. 2017; 60: 24–31.
  32. Wang Z, Hou Y, Yao Z, et al. Expressivity of Interleukin-8 and Gastric Cancer Prognosis Susceptibility: A Systematic Review and Meta-Analysis. Dose Response. 2021; 19(3): 15593258211037127.