Skip to main content
SpringerLink
Log in

Impact of HLA-E gene polymorphism on HLA-E expression in tumor cells and prognosis in patients with stage III colorectal cancer

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

Abstract

Human leukocyte antigen (HLA)-E can contribute to the escape of cancer cells from host immune mechanisms. However, it is unknown whether HLA-E gene polymorphisms might play a role in cancer immune escape. This study aimed to evaluate the correlation between HLA-E gene polymorphisms and HLA-E expression in tumor tissue and determine the effects on clinical outcome of patients with stage III colorectal cancer. Two hundred thirty patients with stage III colorectal cancer were enrolled. HLA-E expression was detected in patient-derived tumor tissues with immunohistochemistry. HLA-E gene alleles in tumor tissues were detected with the polymerase chain reaction–sequence-specific primer method. In colorectal cancer tissue and in the normal tissue adjacent to the tumor, the HLA-E expression rates were 72.2 and 15.1 %, respectively (P < 0.05). Patients with overexpression, low expression, and no expression of HLA-E exhibited disease-free survival of 55.3, 72.9, and 72.1 %, respectively. Patients with HLA-E overexpression exhibited the lowest long-term survival rate. No relationship was observed between the type of HLA-E gene polymorphism and its expression level in tumor tissues; moreover, no polymorphisms appeared to affect the long-term survival of patients with colorectal cancer. The type of HLA-E polymorphism did not have an impact on HLA-E expression in tumors or the prognosis in patients with stage III colorectal cancer. However, the level of HLA-E expression in tumor tissue strongly predicted long-term survival in these patients.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Golfinopoulos V, Salanti G, Pavlidis N, et al. Survival and disease-progression benefits with treatment regimens for advanced colorectal cancer: a meta-analysis. Lancet Oncol. 2007;8(10):898–911.

    Article  PubMed  CAS  Google Scholar 

  2. Morris EJ, Maughan NJ, Forman D, et al. Identifying stage III colorectal cancer patients: the influence of the patient, surgeon, and pathologist. J Clin Oncol. 2007;25(18):2573–9.

    Article  PubMed  Google Scholar 

  3. Iinuma H, Watanabe T, Mimori K, et al. Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes’ stage B and C colorectal cancer. J Clin Oncol. 2011;29(12):1547–55.

    Article  PubMed  Google Scholar 

  4. Bernal M, García-Alcalde F, Concha A, et al. Genome-wide differential genetic profiling characterizes colorectal cancers with genetic instability and specific routes to HLA class I loss and immune escape. Cancer Immunol Immunother. 2012;61(6):803–16.

    Article  PubMed  CAS  Google Scholar 

  5. Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology. 2007;121(1):1–14.

    Article  PubMed  CAS  Google Scholar 

  6. Palmisano GL, Contardi E, Morabito A, et al. HLA-E surface expression is independent of the availability of HLA class I signal sequence-derived peptides in human tumor cell lines. Hum Immunol. 2005;66(1):1–12.

    Article  PubMed  CAS  Google Scholar 

  7. Petrie EJ, Clements CS, Lin J, et al. CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence. J Exp Med. 2008;205(3):725–35.

    Article  PubMed  CAS  Google Scholar 

  8. Wischhusen J, Friese MA, Mittelbronn M, et al. HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo. J Neuropathol Exp Neurol. 2005;64(6):523–8.

    PubMed  CAS  Google Scholar 

  9. Bossard C, Bézieau S, Matysiak-Budnik T, et al. HLA-E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression. Int J Cancer. 2012;131(4):855–63.

    Article  PubMed  CAS  Google Scholar 

  10. Grimsley C, Ober C. Population genetic studies of HLA-E: evidence for selection. Hum Immunol. 1997;52(1):33–40.

    Article  PubMed  CAS  Google Scholar 

  11. O’Callaghan CA, Bell JI. Structure and function of the human MHC class Ib molecules HLA-E, HLA-F and HLA-G. Immunol Rev. 1998;163:129–38.

    Article  PubMed  Google Scholar 

  12. Arnaiz-Villena A, Vargas-Alarcon G, Serrano-Vela JI, et al. HLA-E polymorphism in Amerindians from Mexico (Mazatecans), Colombia (Wayu) and Chile (Mapuches): evolution of MHC-E gene. Tissue Antigens. 2007;69(Suppl 1):132–5.

    Article  PubMed  CAS  Google Scholar 

  13. Matte C, Lacaille J, Zijenah L, et al. HLA-G and HLA-E polymorphisms in an indigenous African population. The ZVITAMBO Study Group. Hum Immunol. 2000;61(11):1150–6.

    Article  PubMed  CAS  Google Scholar 

  14. Veiga-Castelli LC, Castelli EC, Mendes CT Jr, et al. Non-classical HLA-E gene variability in Brazilians: a nearly invariable locus surrounded by the most variable genes in the human genome. Tissue Antigens. 2012;79(1):15–24.

    Article  PubMed  CAS  Google Scholar 

  15. Kunisada T, Moseley JM, Slavin JL, et al. Co-expression of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor in cartilaginous tumours: a marker for malignancy? Pathology. 2002;34(2):133–7.

    Article  PubMed  Google Scholar 

  16. Guo M, Sneige N, Silva EG, et al. Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma. Mod Pathol. 2007;20(2):256–66.

    Article  PubMed  CAS  Google Scholar 

  17. Grimsley C, Kawasaki A, Gassner C, et al. Definitive high resolution typing of HLA-E allelic polymorphisms: identifying potential errors in existing allele data. Tissue Antigens. 2002;60(3):206–12.

    Article  PubMed  CAS  Google Scholar 

  18. Carretero R, Romero JM, Ruiz-Cabello F, et al. Analysis of HLA class I expression in progressing and regressing metastatic melanoma lesions after immunotherapy. Immunogenetics. 2008;60(8):439–47.

    Article  PubMed  CAS  Google Scholar 

  19. Maki G, Hayes GM, Naji A, et al. NK resistance of tumor cells from multiple myeloma and chronic lymphocytic leukemia patients: implication of HLA-G. Leukemia. 2008;22(5):998–1006.

    Article  PubMed  CAS  Google Scholar 

  20. Brooks AG, Borrego F, Posch PE, et al. 18. Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells. J Immunol. 1999;162(1):305–13.

    PubMed  CAS  Google Scholar 

  21. Derré L, Corvaisier M, Charreau B, et al. Expression and release of HLA-E by melanoma cells and melanocytes: potential impact on the response of cytotoxic effector cells. J Immunol. 2006;177(5):3100–7.

    PubMed  Google Scholar 

  22. Malmberg KJ, Levitsky V, Norell H, et al. IFN-gamma protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism. J Clin Invest. 2002;110(10):1515–23.

    PubMed  CAS  Google Scholar 

  23. Kren L, Slaby O, Muckova K, et al. Expression of immune-modulatory molecules HLA-G and HLA-E by tumor cells in glioblastomas: an unexpected prognostic significance? Neuropathology. 2011;31(2):129–34.

    Article  PubMed  Google Scholar 

  24. Dutta N, Majumder D, Gupta A, et al. Analysis of human lymphocyte antigen class I expression in gastric cancer by reverse transcriptase-polymerase chain reaction. Hum Immunol. 2005;66(2):164–9.

    Article  PubMed  CAS  Google Scholar 

  25. de Kruijf EM, Sajet A, van Nes JG, et al. HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol. 2010;185(12):7452–9.

    Article  PubMed  Google Scholar 

  26. Gooden M, Lampen M, Jordanova ES, et al. HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8+ T lymphocytes. Proc Natl Acad Sci USA. 2011;108(26):10656–61.

    Article  PubMed  CAS  Google Scholar 

  27. Levy EM, Sycz G, Arriaga JM, et al. Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells. Innate Immun. 2009;15(2):91–100.

    Article  PubMed  CAS  Google Scholar 

  28. Hirankarn N, Kimkong I, Mutirangura A. HLA-E polymorphism in patients with nasopharyngeal carcinoma. Tissue Antigens. 2004;64(5):588–92.

    Article  PubMed  CAS  Google Scholar 

  29. Liu XX, Pan FH, Tian W. Characterization of HLA-E polymorphism in four distinct populations in Mainland China. Tissue Antigens. 2012;80(1):26–35.

    Article  PubMed  CAS  Google Scholar 

  30. Strong RK, Holmes MA, Li P, et al. HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal stabilities. J Biol Chem. 2003;278(7):5082–90.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by Science and Technology Planning Project of Guangdong Province, China (No. 2007B031513005).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China

    Zi-Jun Zhen, Jia-Yu Ling, Yue Cai, Wen-Biao Luo & You-Jian He

Authors
  1. Zi-Jun Zhen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jia-Yu Ling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yue Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen-Biao Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. You-Jian He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zi-Jun Zhen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhen, ZJ., Ling, JY., Cai, Y. et al. Impact of HLA-E gene polymorphism on HLA-E expression in tumor cells and prognosis in patients with stage III colorectal cancer. Med Oncol 30, 482 (2013). https://doi.org/10.1007/s12032-013-0482-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0482-2

Keywords

Search

Navigation