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

open access

Page views 5980
Article views/downloads 745
Get Citation

Connect on Social Media

Connect on Social Media

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.

Article available in PDF format

View PDF Download PDF file

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.