title: 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.affiliation: a Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education) ; Shihezi University School of Medicine ; Shihezi , China.
authors.forename: Jian Ming
authors.initials: JM
authors.lastname: Hu
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Yun Zhao
authors.initials: YZ
authors.lastname: Chen
authors.forename: Chunxia
authors.initials: C
authors.lastname: Liu
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Cui
authors.forename: Liang
authors.initials: L
authors.lastname: Yin
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Zou
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Cao
authors.forename: Jinfang
authors.initials: J
authors.lastname: Jiang
authors.forename: Weihua
authors.initials: W
authors.lastname: Liang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007623:Kazakhstan; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
keywords: ACN, cancer adjacent normal; CIITA, class II transactivator; CpG, CG dinucleotides; DNA methylation; EC, Esophageal carcinoma; ESCC, esophageal squamous cell carcinoma; Esophageal squamous cell carcinoma; HLA; HLA-II, Human leukocyte antigen II; HPV, human papillomavirus; IHC, Immunohistochemistry; Kazakh; MHC, major histocompatibility complex; Massarray; NE, normal esophageal tissues