HLA-DRB1 and HLA-DQB1 methylation changes promote the occurrence and progression of Kazakh ESCC.

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.

• 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
• Journal: Epigenetics (Epigenetics) Vol. 9 Issue 10 Pg. 1366-73 (Oct 2014) ISSN: 1559-2308 [Electronic] United States
• PMID: 25437052 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• HLA-DRB1 Chains

Topics

• Adult
• Aged
• Carcinoma, Squamous Cell (ethnology, genetics)
• Case-Control Studies
• DNA Methylation
• Epigenesis, Genetic
• Esophageal Neoplasms (ethnology, genetics)
• Esophageal Squamous Cell Carcinoma
• Female
• HLA-DQ beta-Chains (genetics)
• HLA-DRB1 Chains (genetics)
• Humans
• Kazakhstan
• Male
• Middle Aged
• Neoplasm Staging
• Promoter Regions, Genetic