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Published in: Cancer Immunology, Immunotherapy 10/2017

01-10-2017 | Original Article

Decreased human leukocyte antigen A*02:01 frequency is associated with risk of glioma and existence of human cytomegalovirus: a case–control study in Northern China

Authors: Sheng Han, Jian Deng, Zixun Wang, Huan Liu, Wen Cheng, Anhua Wu

Published in: Cancer Immunology, Immunotherapy | Issue 10/2017

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Abstract

Background

Human leukocyte antigens (HLAs) play an important role in host defense against viral infection and tumorigenesis. Human cytomegalovirus (HCMV) has been linked to glioma development. This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population.

Methods

The study population included 150 glioma patients and 150 tumor-free brain injury control subjects (control-A) matched according to geography, ethnicity, age, and gender. HLA allele frequency was compared between the two groups using peripheral blood samples by PCR sequence-based typing. These data were also compared with HLA frequencies obtained from a Northern Chinese Han population database (control-B). HCMV DNA was detected in the peripheral blood of glioma patients and control group-A by nested PCR. The expression of HCMV proteins IE1-72 and pp65 in tumor tissues was evaluated by immunohistochemistry.

Results

The frequency of HLA-A*02:01 was decreased in glioma patients as compared to control group-A and -B (P < 0.001 and P = 0.001, respectively). The age/sex-adjusted odds ratio for HLA-A*02:01 positivity vs. negativity was 0.392 (95% confidence interval 0.225–0.683). HCMV was more frequently detected in the peripheral blood and tumor tissue of HLA-A*02:01-negative glioma patients. HLA-A*02:01 and HCMV were not associated with overall survival.

Conclusion

There is a correlation between decreased HLA-A*0201 allele frequency and glioma susceptibility.
Appendix
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Literature
1.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996CrossRefPubMed
2.
go back to reference Baumgarten P, Michaelis M, Rothweiler F, Starzetz T, Rabenau HF et al (2014) Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics. Neuro Oncol 16:1469–1477CrossRefPubMedPubMedCentral Baumgarten P, Michaelis M, Rothweiler F, Starzetz T, Rabenau HF et al (2014) Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics. Neuro Oncol 16:1469–1477CrossRefPubMedPubMedCentral
3.
go back to reference Strong MJ, Blanchard E 4th, Lin Z, Morris CA, Baddoo M et al (2016) A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus—tumor association. Acta Neuropathol Commun 4:71CrossRefPubMedPubMedCentral Strong MJ, Blanchard E 4th, Lin Z, Morris CA, Baddoo M et al (2016) A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus—tumor association. Acta Neuropathol Commun 4:71CrossRefPubMedPubMedCentral
4.
go back to reference Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A et al (2008) Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol 10:10–18CrossRefPubMedPubMedCentral Mitchell DA, Xie W, Schmittling R, Learn C, Friedman A et al (2008) Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol 10:10–18CrossRefPubMedPubMedCentral
5.
go back to reference Ding D, Han S, Wang Z, Guo Z, Wu A (2014) Does the existence of HCMV components predict poor prognosis in glioma. J Neurooncol 116:515–522CrossRefPubMed Ding D, Han S, Wang Z, Guo Z, Wu A (2014) Does the existence of HCMV components predict poor prognosis in glioma. J Neurooncol 116:515–522CrossRefPubMed
6.
go back to reference Dziurzynski K, Chang SM, Heimberger AB, Kalejta RF, McGregor DSR et al (2012) Consensus on the role of human cytomegalovirus in glioblastoma. Neuro Oncol 14:246–255CrossRefPubMedPubMedCentral Dziurzynski K, Chang SM, Heimberger AB, Kalejta RF, McGregor DSR et al (2012) Consensus on the role of human cytomegalovirus in glioblastoma. Neuro Oncol 14:246–255CrossRefPubMedPubMedCentral
7.
go back to reference Mohammad AA, Rahbar A, Lui WO, Davoudi B, Catrina A et al (2014) Detection of circulating hcmv-miR-UL112-3p in patients with glioblastoma, rheumatoid arthritis, diabetes mellitus and healthy controls. PLoS One 9:e113740CrossRefPubMedPubMedCentral Mohammad AA, Rahbar A, Lui WO, Davoudi B, Catrina A et al (2014) Detection of circulating hcmv-miR-UL112-3p in patients with glioblastoma, rheumatoid arthritis, diabetes mellitus and healthy controls. PLoS One 9:e113740CrossRefPubMedPubMedCentral
8.
go back to reference dos Santos CJ, Stangherlin LM, Figueiredo EG, Correa C, Teixeira MJ, da Silva MC (2014) High prevalence of HCMV and viral load in tumor tissues and peripheral blood of glioblastoma multiforme patients. J Med Virol 86:1953–1961CrossRefPubMed dos Santos CJ, Stangherlin LM, Figueiredo EG, Correa C, Teixeira MJ, da Silva MC (2014) High prevalence of HCMV and viral load in tumor tissues and peripheral blood of glioblastoma multiforme patients. J Med Virol 86:1953–1961CrossRefPubMed
9.
go back to reference Fajfr M, Stepanova V (2013) Cytomegalovirus and its relationship to chronic inflammatory bowel diseases and tumors. Klin Mikrobiol Infekc Lek 19:103–106PubMed Fajfr M, Stepanova V (2013) Cytomegalovirus and its relationship to chronic inflammatory bowel diseases and tumors. Klin Mikrobiol Infekc Lek 19:103–106PubMed
10.
go back to reference Cobbs CS (2013) Cytomegalovirus and brain tumor: epidemiology, biology and therapeutic aspects. Curr Opin Oncol 25:682–688CrossRefPubMed Cobbs CS (2013) Cytomegalovirus and brain tumor: epidemiology, biology and therapeutic aspects. Curr Opin Oncol 25:682–688CrossRefPubMed
11.
go back to reference Price RL, Song J, Bingmer K, Kim TH, Yi JY et al (2013) Cytomegalovirus contributes to glioblastoma in the context of tumor suppressor mutations. Cancer Res 73:3441–3450CrossRefPubMedPubMedCentral Price RL, Song J, Bingmer K, Kim TH, Yi JY et al (2013) Cytomegalovirus contributes to glioblastoma in the context of tumor suppressor mutations. Cancer Res 73:3441–3450CrossRefPubMedPubMedCentral
12.
go back to reference Zhang HG, Pang XW, Shang XY, Xing Q, Chen WF (2003) Functional supertype of HLA-A2 in the presentation of Flu matrix p58–66 to induce CD8+ T-cell response in a Northern Chinese population. Tissue Antigens 62:285–295CrossRefPubMed Zhang HG, Pang XW, Shang XY, Xing Q, Chen WF (2003) Functional supertype of HLA-A2 in the presentation of Flu matrix p58–66 to induce CD8+ T-cell response in a Northern Chinese population. Tissue Antigens 62:285–295CrossRefPubMed
13.
go back to reference La Torre D, Maugeri R, Angileri FF, Pezzino G, Conti A et al (2009) Human leukocyte antigen frequency in human high-grade gliomas: a case–control study in Sicily. Neurosurgery 64:1082–1088 (discussion 1088–1089) CrossRefPubMed La Torre D, Maugeri R, Angileri FF, Pezzino G, Conti A et al (2009) Human leukocyte antigen frequency in human high-grade gliomas: a case–control study in Sicily. Neurosurgery 64:1082–1088 (discussion 1088–1089) CrossRefPubMed
14.
go back to reference Hou TY, Chen HC, Chen CH, Chang DM, Liu FC, Lai JH (2007) Usefulness of human leucocyte antigen-B27 subtypes in predicting ankylosing spondylitis: Taiwan experience. Intern Med J 37:749–752PubMed Hou TY, Chen HC, Chen CH, Chang DM, Liu FC, Lai JH (2007) Usefulness of human leucocyte antigen-B27 subtypes in predicting ankylosing spondylitis: Taiwan experience. Intern Med J 37:749–752PubMed
15.
go back to reference Ballerini C, Guerini FR, Rombola G, Rosati E, Massacesi L et al (2004) HLA-multiple sclerosis association in continental Italy and correlation with disease prevalence in Europe. J Neuroimmunol 150:178–185CrossRefPubMed Ballerini C, Guerini FR, Rombola G, Rosati E, Massacesi L et al (2004) HLA-multiple sclerosis association in continental Italy and correlation with disease prevalence in Europe. J Neuroimmunol 150:178–185CrossRefPubMed
16.
go back to reference Gonzalez-Gay MA, Garcia-Porrua C, Hajeer AH (2002) Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of rheumatoid arthritis. Semin Arthritis Rheum 31:355–360CrossRefPubMed Gonzalez-Gay MA, Garcia-Porrua C, Hajeer AH (2002) Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of rheumatoid arthritis. Semin Arthritis Rheum 31:355–360CrossRefPubMed
17.
go back to reference Luongo V, Pirozzi G, Caraco C, Errico S, de Angelis F et al (2004) HLA allele frequency and clinical outcome in Italian patients with cutaneous melanoma. Tissue Antigens 64:84–87CrossRefPubMed Luongo V, Pirozzi G, Caraco C, Errico S, de Angelis F et al (2004) HLA allele frequency and clinical outcome in Italian patients with cutaneous melanoma. Tissue Antigens 64:84–87CrossRefPubMed
18.
go back to reference Ohtani M, Azuma T, Yamazaki S, Yamakawa A, Ito Y et al (2003) Association of the HLA-DRB1 gene locus with gastric adenocarcinoma in Japan. Dig Liver Dis 35:468–472CrossRefPubMed Ohtani M, Azuma T, Yamazaki S, Yamakawa A, Ito Y et al (2003) Association of the HLA-DRB1 gene locus with gastric adenocarcinoma in Japan. Dig Liver Dis 35:468–472CrossRefPubMed
19.
go back to reference Younger AR, Amria S, Jeffrey WA, Mahdy AE, Goldstein OG et al (2008) HLA class II antigen presentation by prostate cancer cells. Prostate Cancer Prostatic Dis 11:334–341CrossRefPubMed Younger AR, Amria S, Jeffrey WA, Mahdy AE, Goldstein OG et al (2008) HLA class II antigen presentation by prostate cancer cells. Prostate Cancer Prostatic Dis 11:334–341CrossRefPubMed
20.
go back to reference Song W, Ruder AM, Hu L, Li Y, Ni R et al (2009) Genetic epidemiology of glioblastoma multiforme: confirmatory and new findings from analyses of human leukocyte antigen alleles and motifs. PLoS One 4:e7157CrossRefPubMedPubMedCentral Song W, Ruder AM, Hu L, Li Y, Ni R et al (2009) Genetic epidemiology of glioblastoma multiforme: confirmatory and new findings from analyses of human leukocyte antigen alleles and motifs. PLoS One 4:e7157CrossRefPubMedPubMedCentral
21.
go back to reference Guerini FR, Agliardi C, Zanzottera M, Delbue S, Pagani E et al (2006) Human leukocyte antigen distribution analysis in North Italian brain Glioma patients: an association with HLA-DRB1*14. J Neurooncol 77:213–217CrossRefPubMed Guerini FR, Agliardi C, Zanzottera M, Delbue S, Pagani E et al (2006) Human leukocyte antigen distribution analysis in North Italian brain Glioma patients: an association with HLA-DRB1*14. J Neurooncol 77:213–217CrossRefPubMed
22.
go back to reference Tang J, Shao W, Dorak MT, Li Y, Miike R et al (2005) Positive and negative associations of human leukocyte antigen variants with the onset and prognosis of adult glioblastoma multiforme. Cancer Epidemiol Biomark Prev 14:2040–2044CrossRef Tang J, Shao W, Dorak MT, Li Y, Miike R et al (2005) Positive and negative associations of human leukocyte antigen variants with the onset and prognosis of adult glioblastoma multiforme. Cancer Epidemiol Biomark Prev 14:2040–2044CrossRef
23.
go back to reference Bassig BA, Inskip PD, Burdette L, Shapiro WR, Selker RG et al (2011) Selected human leukocyte antigen class II polymorphisms and risk of adult glioma. J Neuroimmunol 233:185–191CrossRefPubMed Bassig BA, Inskip PD, Burdette L, Shapiro WR, Selker RG et al (2011) Selected human leukocyte antigen class II polymorphisms and risk of adult glioma. J Neuroimmunol 233:185–191CrossRefPubMed
24.
go back to reference Krausa P, Brywka M 3rd, Savage D, Hui KM, Bunce M et al (1995) Genetic polymorphism within HLA-A*02: significant allelic variation revealed in different populations. Tissue Antigens 45:223–231CrossRefPubMed Krausa P, Brywka M 3rd, Savage D, Hui KM, Bunce M et al (1995) Genetic polymorphism within HLA-A*02: significant allelic variation revealed in different populations. Tissue Antigens 45:223–231CrossRefPubMed
25.
go back to reference Liang B, Zhu L, Liang Z, Weng X, Lu X et al (2006) A simplified PCR-SSP method for HLA-A2 subtype in a population of Wuhan, China. Cell Mol Immunol 3:453–458PubMed Liang B, Zhu L, Liang Z, Weng X, Lu X et al (2006) A simplified PCR-SSP method for HLA-A2 subtype in a population of Wuhan, China. Cell Mol Immunol 3:453–458PubMed
26.
go back to reference Yang G, Deng YJ, Hu SN, Wu DY, Li SB et al (2006) HLA-A, -B, and -DRB1 polymorphism defined by sequence-based typing of the Han population in Northern China. Tissue Antigens 67:146–152CrossRefPubMed Yang G, Deng YJ, Hu SN, Wu DY, Li SB et al (2006) HLA-A, -B, and -DRB1 polymorphism defined by sequence-based typing of the Han population in Northern China. Tissue Antigens 67:146–152CrossRefPubMed
27.
go back to reference Deng Z, Wang D, Xu Y, Gao S, Zhou H et al (2010) HLA-C polymorphisms and PCR dropout in exons 2 and 3 of the Cw*0706 allele in sequence-based typing for unrelated Chinese marrow donors. Hum Immunol 71:577–581CrossRefPubMed Deng Z, Wang D, Xu Y, Gao S, Zhou H et al (2010) HLA-C polymorphisms and PCR dropout in exons 2 and 3 of the Cw*0706 allele in sequence-based typing for unrelated Chinese marrow donors. Hum Immunol 71:577–581CrossRefPubMed
28.
go back to reference Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R (2008) Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol 116:79–86CrossRefPubMedPubMedCentral Scheurer ME, Bondy ML, Aldape KD, Albrecht T, El-Zein R (2008) Detection of human cytomegalovirus in different histological types of gliomas. Acta Neuropathol 116:79–86CrossRefPubMedPubMedCentral
29.
go back to reference Cobbs CS, Matlaf L, Harkins LE (2014) Methods for the detection of cytomegalovirus in glioblastoma cells and tissues. Methods Mol Biol 1119:165–196CrossRefPubMed Cobbs CS, Matlaf L, Harkins LE (2014) Methods for the detection of cytomegalovirus in glioblastoma cells and tissues. Methods Mol Biol 1119:165–196CrossRefPubMed
30.
go back to reference Sjostrom S, Hjalmars U, Juto P, Wadell G, Hallmans G et al (2011) Human immunoglobulin G levels of viruses and associated glioma risk. Cancer Causes Control 22:1259–1266CrossRefPubMedPubMedCentral Sjostrom S, Hjalmars U, Juto P, Wadell G, Hallmans G et al (2011) Human immunoglobulin G levels of viruses and associated glioma risk. Cancer Causes Control 22:1259–1266CrossRefPubMedPubMedCentral
31.
go back to reference Amirian ES, Marquez-Do D, Bondy ML, Scheurer ME (2013) Anti-human-cytomegalovirus immunoglobulin G levels in glioma risk and prognosis. Cancer Med 2:57–62CrossRefPubMed Amirian ES, Marquez-Do D, Bondy ML, Scheurer ME (2013) Anti-human-cytomegalovirus immunoglobulin G levels in glioma risk and prognosis. Cancer Med 2:57–62CrossRefPubMed
33.
34.
go back to reference Okano F, Storkus WJ, Chambers WH, Pollack IF, Okada H (2002) Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain. Clin Cancer Res 8:2851–2855PubMed Okano F, Storkus WJ, Chambers WH, Pollack IF, Okada H (2002) Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain. Clin Cancer Res 8:2851–2855PubMed
35.
go back to reference Ji J, Judkowski VA, Liu G, Wang H, Bunying A et al (2014) Identification of novel human leukocyte antigen-A*0201-restricted, cytotoxic T lymphocyte epitopes on CD133 for cancer stem cell immunotherapy. Stem Cells Transl Med 3:356–364CrossRefPubMed Ji J, Judkowski VA, Liu G, Wang H, Bunying A et al (2014) Identification of novel human leukocyte antigen-A*0201-restricted, cytotoxic T lymphocyte epitopes on CD133 for cancer stem cell immunotherapy. Stem Cells Transl Med 3:356–364CrossRefPubMed
36.
go back to reference Myers CE, Hanavan P, Antwi K, Mahadevan D, Nadeem AJ et al (2011) CTL recognition of a novel HLA-A*0201-binding peptide derived from glioblastoma multiforme tumor cells. Cancer Immunol Immunother 60:1319–1332CrossRefPubMed Myers CE, Hanavan P, Antwi K, Mahadevan D, Nadeem AJ et al (2011) CTL recognition of a novel HLA-A*0201-binding peptide derived from glioblastoma multiforme tumor cells. Cancer Immunol Immunother 60:1319–1332CrossRefPubMed
37.
go back to reference Frigerio S, Ciusani E, Pozzi A, Silvani A, Salmaggi A, Boiardi A (1999) Tumor necrosis factor microsatellite polymorphisms in Italian glioblastoma patients. Cancer Genet Cytogenet 109:172–174CrossRefPubMed Frigerio S, Ciusani E, Pozzi A, Silvani A, Salmaggi A, Boiardi A (1999) Tumor necrosis factor microsatellite polymorphisms in Italian glioblastoma patients. Cancer Genet Cytogenet 109:172–174CrossRefPubMed
38.
go back to reference Li R, Zhao Y, Fan W, Chen H, Chen Y et al (2011) Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population. Int J Cancer 128:166–175CrossRefPubMed Li R, Zhao Y, Fan W, Chen H, Chen Y et al (2011) Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population. Int J Cancer 128:166–175CrossRefPubMed
39.
go back to reference Yin D, Ogawa S, Kawamata N, Tunici P, Finocchiaro G et al (2009) High-resolution genomic copy number profiling of glioblastoma multiforme by single nucleotide polymorphism DNA microarray. Mol Cancer Res 7:665–677CrossRefPubMed Yin D, Ogawa S, Kawamata N, Tunici P, Finocchiaro G et al (2009) High-resolution genomic copy number profiling of glioblastoma multiforme by single nucleotide polymorphism DNA microarray. Mol Cancer Res 7:665–677CrossRefPubMed
40.
go back to reference Tenan M, Carrara F, DiDonato S, Finocchiaro G (1995) Absence of mutations and identification of two polymorphisms in the SSCP and sequence analysis of p21CKI gene in malignant gliomas. Int J Cancer 62:115–117CrossRefPubMed Tenan M, Carrara F, DiDonato S, Finocchiaro G (1995) Absence of mutations and identification of two polymorphisms in the SSCP and sequence analysis of p21CKI gene in malignant gliomas. Int J Cancer 62:115–117CrossRefPubMed
41.
go back to reference Tussey LG, Matsui M, Rowland-Jones S, Warburton R, Frelinger JA, McMichael A (1994) Analysis of mutant HLA-A2 molecules. Differential effects on peptide binding and CTL recognition. J Immunol 152:1213–1221PubMed Tussey LG, Matsui M, Rowland-Jones S, Warburton R, Frelinger JA, McMichael A (1994) Analysis of mutant HLA-A2 molecules. Differential effects on peptide binding and CTL recognition. J Immunol 152:1213–1221PubMed
42.
go back to reference Zou Y, Bresnahan W, Taylor RT, Stastny P (2005) Effect of human cytomegalovirus on expression of MHC class I-related chains A. J Immunol 174:3098–3104CrossRefPubMed Zou Y, Bresnahan W, Taylor RT, Stastny P (2005) Effect of human cytomegalovirus on expression of MHC class I-related chains A. J Immunol 174:3098–3104CrossRefPubMed
43.
44.
go back to reference Schuessler A, Smith C, Beagley L, Boyle GM, Rehan S et al (2014) Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Res 74:3466–3476CrossRefPubMed Schuessler A, Smith C, Beagley L, Boyle GM, Rehan S et al (2014) Autologous T-cell therapy for cytomegalovirus as a consolidative treatment for recurrent glioblastoma. Cancer Res 74:3466–3476CrossRefPubMed
45.
go back to reference Stragliotto G, Rahbar A, Solberg NW, Lilja A, Taher C et al (2013) Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, hypothesis-generating study. Int J Cancer 133:1204–1213CrossRefPubMed Stragliotto G, Rahbar A, Solberg NW, Lilja A, Taher C et al (2013) Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, hypothesis-generating study. Int J Cancer 133:1204–1213CrossRefPubMed
Metadata
Title
Decreased human leukocyte antigen A*02:01 frequency is associated with risk of glioma and existence of human cytomegalovirus: a case–control study in Northern China
Authors
Sheng Han
Jian Deng
Zixun Wang
Huan Liu
Wen Cheng
Anhua Wu
Publication date
01-10-2017
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 10/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-017-2018-7

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