HLA-DRB1 and HLA-DQB1 Methylation Changes Promote the Occurrence and Progression of Kazakh ESCC

Overview

Journal Epigenetics

Specialty Genetics

Date 2014 Dec 2

PMID 25437052

Citations 13

Authors

Jian Ming Hu

Ling Li

Yun Zhao Chen

Chunxia Liu

Xiaobin Cui

Liang Yin

Lan Yang

Hong Zou

Lijuan Pang

Jin Zhao

Yan Qi

Yuwen Cao

Jinfang Jiang

Weihua Liang

Feng Li

Affiliations

Soon will be listed here.

Abstract

Human leukocyte antigen II (HLA-II) plays an important role in host immune responses to cancer cells. Changes in gene methylation may result in aberrant expression of HLA-II, serving a key role in the pathogenesis of Kazakh esophageal squamous cell carcinoma (ESCC). We analyzed the expression level of HLA-II (HLA-DP, -DQ, and -DR) by immunohistochemistry, as well as the methylation status of HLA-DRB1 and HLA-DQB1 by MassARRAY spectrometry in Xinjiang Kazakh ESCC. Expression of HLA-II in ESCC was significantly higher than that in cancer adjacent normal (ACN) samples (P < 0.05). Decreased HLA-II expression was closely associated with later clinical stages of ESCC (P < 0.05). Hypomethylation of HLA-DRB1 and hypermethylation of HLA-DQB1 was significantly correlated with occurrence of Kazakh ESCC (P < 0.01), and mainly manifested as hypomethylation of CpG9, CpG10-11, and CpG16 in HLA-DRB1 and hypermethylation of CpG6-7 and CpG16-17 in HLA-DQB1 (P < 0.01). Moreover, hypomethylation of HLA-DQB1 CpG6-7 correlated with poor differentiation in ESCCs, whereas hypermethylation of HLA-DRB1 CpG16 and hypomethylation of HLA-DQB1 CpG16-17 were significantly associated with later stages of ESCC (P < 0.05). A significant inverse association between HLA-DRB1 CpG9 methylation and HLA-II expression was found in ESCC (P < 0.05). These findings suggest aberrant HLA-DRB1 and HLA-DQB1 methylation contributes to the aberrant expression of HLA-II. These molecular changes may influence the immune response to specific tumor epitopes, promoting the occurrence and progression of Kazakh ESCC.

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References

Chang C, Flavell R . Class II transactivator regulates the expression of multiple genes involved in antigen presentation. J Exp Med. 1995; 181(2):765-7. PMC: 2191893. DOI: 10.1084/jem.181.2.765. View

Shi S, Cote R, Wu L, Liu C, Datar R, Shi Y . DNA extraction from archival formalin-fixed, paraffin-embedded tissue sections based on the antigen retrieval principle: heating under the influence of pH. J Histochem Cytochem. 2002; 50(8):1005-11. DOI: 10.1177/002215540205000802. View

Jordanova E, Philippo K, Giphart M, Schuuring E, Kluin P . Mutations in the HLA class II genes leading to loss of expression of HLA-DR and HLA-DQ in diffuse large B-cell lymphoma. Immunogenetics. 2003; 55(4):203-9. DOI: 10.1007/s00251-003-0563-z. View

Wang C, Cicek M, Charbonneau B, Kalli K, Armasu S, Larson M . Tumor hypomethylation at 6p21.3 associates with longer time to recurrence of high-grade serous epithelial ovarian cancer. Cancer Res. 2014; 74(11):3084-91. PMC: 4054691. DOI: 10.1158/0008-5472.CAN-13-3198. View

Ting J, Trowsdale J . Genetic control of MHC class II expression. Cell. 2002; 109 Suppl:S21-33. DOI: 10.1016/s0092-8674(02)00696-7. View

Baccar A, Ferchichi I, Troudi W, Marrakchi R, Ben Hmida N, Jebini S . CD99 and HLA-II immunostaining in breast cancer tissue and their correlation with lymph node metastasis. Dis Markers. 2013; 34(5):363-71. PMC: 3810233. DOI: 10.3233/DMA-130982. View

Hu J, Li L, Pang L, Chen Y, Yang L, Liu C . HLA-DRB1*1501 and HLA-DQB1*0301 alleles are positively associated with HPV16 infection-related Kazakh esophageal squamous cell carcinoma in Xinjiang China. Cancer Immunol Immunother. 2012; 61(11):2135-41. PMC: 11029737. DOI: 10.1007/s00262-012-1281-x. View

Kollaee A, Ghaffarpor M, Ghlichnia H, Ghaffari S, Zamani M . The influence of the HLA-DRB1 and HLA-DQB1 allele heterogeneity on disease risk and severity in Iranian patients with multiple sclerosis. Int J Immunogenet. 2012; 39(5):414-22. DOI: 10.1111/j.1744-313X.2012.01104.x. View

Steidl C, Shah S, Woolcock B, Rui L, Kawahara M, Farinha P . MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature. 2011; 471(7338):377-81. PMC: 3902849. DOI: 10.1038/nature09754. View

10.

Thompson R, Suzuki M, Lau K, Greally J . A pipeline for the quantitative analysis of CG dinucleotide methylation using mass spectrometry. Bioinformatics. 2009; 25(17):2164-70. PMC: 2800352. DOI: 10.1093/bioinformatics/btp382. View

11.

Cheung W, Liu G . Genetic variations in esophageal cancer risk and prognosis. Gastroenterol Clin North Am. 2009; 38(1):75-91, viii. DOI: 10.1016/j.gtc.2009.01.009. View

12.

Xie X, Mei M, Liao W, Qian L, Yu X, Fei R . Expression of CIITA-related MHCII molecules in tumors linked to prognosis in hepatocellular carcinoma. Int J Oncol. 2009; 34(3):681-8. DOI: 10.3892/ijo_00000194. View

13.

Radpour R, Montazer Haghighi M, Fan A, Torbati P, Hahn S, Holzgreve W . High-throughput hacking of the methylation patterns in breast cancer by in vitro transcription and thymidine-specific cleavage mass array on MALDI-TOF silico-chip. Mol Cancer Res. 2008; 6(11):1702-9. DOI: 10.1158/1541-7786.MCR-08-0262. View

14.

De Lerma Barbaro A, De Ambrosis A, Banelli B, Li Pira G, Aresu O, Romani M . Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-gamma in promyelocytic cells. Int Immunol. 2008; 20(11):1457-66. PMC: 2572003. DOI: 10.1093/intimm/dxn103. View

15.

Madeleine M, Johnson L, Smith A, Hansen J, Nisperos B, Li S . Comprehensive analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci and squamous cell cervical cancer risk. Cancer Res. 2008; 68(9):3532-9. PMC: 2662593. DOI: 10.1158/0008-5472.CAN-07-6471. View

16.

Jo Y, Lee J, Li S, Choi Y, Bai Y, Kim Y . Significance of the expression of major histocompatibility complex class II antigen, HLA-DR and -DQ, with recurrence of papillary thyroid cancer. Int J Cancer. 2007; 122(4):785-90. DOI: 10.1002/ijc.23167. View

17.

Zhou J, Ye F, Chen H, Zhou C, Lu W, Xie X . Altered expression of cellular membrane molecules of HLA-DR, HLA-G and CD99 in cervical intraepithelial neoplasias and invasive squamous cell carcinoma. Life Sci. 2006; 78(22):2643-9. DOI: 10.1016/j.lfs.2005.10.039. View

18.

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

19.

Mota F, Rayment N, Chong S, Singer A, Chain B . The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium. Clin Exp Immunol. 1999; 116(1):33-40. PMC: 1905217. DOI: 10.1046/j.1365-2249.1999.00826.x. View

20.

Sumiyoshi K, Kuwano H, Watanabe M, Kitamura M, Toh Y, Sugimachi K . HLA-DR antigen expression in squamous epithelial dysplasia and squamous cell carcinoma of the esophagus: an immunohistochemical study. Oncol Rep. 1999; 6(2):301-6. DOI: 10.3892/or.6.2.301. View