Skip to main content

Advertisement

SpringerLink
Log in

Overexpression of interleukin-8 receptor 2 (IL-8R2) indicates better prognosis in esophageal adenocarcinoma and squamous cell carcinoma procession

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Researches have showed that interleukin family or receptors play a role in many human tumor progressions including esophageal carcinoma. In this study, we examined the expression of interleukin-8 receptor 2 (IL-8R2) and analyze the relationship between it and esophageal carcinoma clinical characteristics. IL-8R2 protein expression was confirmed by immunohistochemistry and immunofluorescence arrays and was analyzed further via Western blot and qRT-PCR analysis in frozen tissues. The correlation between their expression levels and clinical characteristics were evaluated by Mann–Whitney and Kruskal–Wallis test. Via Kaplan–Meier plots and Cox proportional hazard models, overall survival (OS) was analyzed. Compared with normal esophageal tissue, IL-8R2 protein was overexpressed significantly in esophageal cancer (p < 0.05) and was observed both in cytoplasm and nuclear. The lower expression of IL-8R2 protein was observed with higher p staging of esophageal cancer, and the significant association between them was confirmed (p = 0.000), and in advanced p T stage, the similar result was obtained (p = 0.015); however, compared with lymph node metastasis-negative group, it is no significant difference in positive group (p = 0.152). In a Kaplan–Meier analysis, compared with IL-8R2 low expression, IL-8R2 high expression identified a group of patients with the longest OS. Cox proportional hazard models revealed that IL-8R2 predicted long time to OS. The higher expression of IL-8R2 was found in early esophageal carcinoma, which may indicate that IL-8R2 plays an important role and is better prognostic factor in esophageal cancer development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50.

    Article  PubMed  Google Scholar 

  2. Daly JM, Fry WA, Little AG, Winchester DP, Mckee RF, Stewart AK, et al. Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study. J Am Coll Surg. 2000;190(5):562–72.

    Article  CAS  PubMed  Google Scholar 

  3. Yamada A, Fujii S, Daiko H, Nishimura M, Chiba T, Ochiai A. Aberrant expression of EZH2 is associated with a poor outcome and P53 alteration in squamous cell carcinoma of the esophagus. Int J Oncol. 2011;38(2):345–53.

    CAS  PubMed  Google Scholar 

  4. Yates M, Cheong E, Luben R, lgali L, Fitzgerald R, Khaw KT, et al. Body Mass Index, Smoking, and Alcohol and Risks of Barrett’s Esophagus and Esophageal Adenocarcinoma: A UK Prospective Cohort Study. Dig Dis Sci. 2014 Feb 6. [Epub ahead of print].

  5. Navarro Silvera SA, Mayne ST, Gammon MD, Vaughan TL, Chow WH, Dubin JA, et al. Diet and lifestyle factors and risk of subtypes of esophageal and gastric cancers: classification tree analysis. Ann Epidemiol. 2014;24(1):50–7.

    Article  PubMed  Google Scholar 

  6. Zeng R, Duan L, Kong Y, Liang Y, Wu X, Wei X, et al. Clinicopathological and prognostic role of MMP-9 in esophageal squamous cell carcinoma: a meta-analysis. Chin J Cancer Res. 2013;25(6):637–45.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Lam TK, Freedman ND, Fan JH, Qiao YL, Dawsey SM, Taylor PR, et al. Prediagnostic plasma vitamin C and risk of gastric adenocarcinoma and esophageal squamous cell carcinoma in a Chinese population. Am J Clin Nutr. 2013;98(5):1289–97.

    Article  CAS  PubMed  Google Scholar 

  8. Noble F, Nolan L, Bateman AC, Byrne JP, Kelly JJ, Bailey IS, et al. Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus. World J Gastroenterol. 2013;19(48):9282–93.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Lou F, Sima CS, Adusumilli PS, Bains MS, Sarkaria IS, Rusch VW, et al. Esophageal cancer recurrence patterns and implications for surveillance. J Thorac Oncol. 2013;8(12):1558–62.

    Article  PubMed  Google Scholar 

  10. Hull J, Thomson A, Kwiatkowski D. Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax. 2000;55(12):1023–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Hull J, Ackerman H, Isles K, Usen S, Pinder M, Thomson A, et al. Unusual haplotypic structure of IL8, a susceptibility locus for a common respiratory virus. Am J Hum Genet. 2001;69(2):413–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Modi WS, Chen ZQ. Localization of the human CXC chemokine subfamily on the long arm of chromosome 4 using radiation hybrids. Genomics. 1998;47(1):136–9.

    Article  CAS  PubMed  Google Scholar 

  13. Green LA, Petrusca D, Rajashekhar G, Gianaris T, Schweitzer KS, Wang L, et al. Cigarette smoke-induced CXCR3 receptor up-regulation mediates endothelial apoptosis. Am J Respir Cell Mol Biol. 2012;47(6):807–14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Jiang WG, Sanders AJ, Ruge F, Harding KG. Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human keratinocytes, the role of PLC-γ and potential clinical implications. Exp Ther Med. 2012;3(2):231–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Sansone P, Storci G, Tavolari S, Guarnieri T, Giovannini C, Taffurelli M, et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest. 2007;117(12):3988–4002.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Waugh DJ, Wilson C. The interleukin-8 pathway in cancer. Clin Cancer Res. 2008;14(21):6735–41.

    Article  CAS  PubMed  Google Scholar 

  17. Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, et al. Assignment of the genes encoding human interleukin-8 receptor types 1 and 2 and an interleukin-8 receptor pseudogene to chromosome 2q35. Genomics. 1992;14(3):685–91.

    Article  CAS  PubMed  Google Scholar 

  18. Mrugacz M, Kaczmarski M, Bakunowicz-Lazarczyk A, Zelazowska B, Wysocka J, Minarowska A. IL-8 and IFN-gamma in tear fluid of patients with cystic fibrosis. J Interferon Cytokine Res. 2006;26(2):71–5.

    Article  CAS  PubMed  Google Scholar 

  19. Wang XB, Jiang XR, Yu XY, Wang L, He S, Feng FY, et al. Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody-based therapy. Cancer Sci. 2014;105(2):176–85.

    Article  CAS  PubMed  Google Scholar 

  20. Sawayama H, Ishimoto T, Watanabe M, Yoshida N, Sugihara H, Kurashige J, et al. Small molecule agonists of PPAR-γ exert therapeutic effects in esophageal cancer. Cancer Res. 2014;74(2):575–85.

    Article  CAS  PubMed  Google Scholar 

  21. Yuan A, Chen JJ, Yao PL, Yang PC. The role of interleukin-8 in cancer cells and microenvironment interaction. Front Biosci. 2005;10:853–65.

    Article  CAS  PubMed  Google Scholar 

  22. Schadendorf D, Möller A, Algermissen B, Worm M, Sticherling M, Czarnetzki BM. IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J Immunol. 1993;151(5):2667–75.

    CAS  PubMed  Google Scholar 

  23. Sharma B, Singh S, Varney ML, Singh RK. Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma. Expert Opin Ther Targets. 2010;14(4):435–42.

    Article  CAS  PubMed  Google Scholar 

  24. Fernando RI, Castillo MD, Litzinger M, Hamilton DH, Palena C. IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells. Cancer Res. 2011;71(15):5296–306.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Chai W, Zhang J, Duan Y, Pan D, Pan D, Liu W, Li Y, et al. Pseudomonas pyocyanin stimulates IL-8 expression through MAPK and NF-kappaB pathways in differentiated U937 cells. BMC Microbiol. 2014;14(1):26.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Conflict of interest

We all read introductions about afflict interest of medical oncology seriously. All authors declare that: not any data or results were submitted or published in other place; we have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in.

Author information

Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Huai He Hospital of He Nan University, Kai-feng, 475000, He-Nan, China

    Bing Liang, Hui Zhao, Jian-Bo Che, Hao-Jie Wang & Gong-Ning Shi

Authors
  1. Bing Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian-Bo Che
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hao-Jie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gong-Ning Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gong-Ning Shi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liang, B., Zhao, H., Che, JB. et al. Overexpression of interleukin-8 receptor 2 (IL-8R2) indicates better prognosis in esophageal adenocarcinoma and squamous cell carcinoma procession. Med Oncol 31, 89 (2014). https://doi.org/10.1007/s12032-014-0089-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0089-2

Keywords

Search

Navigation