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Epigenetic Changes within the Promoter Regions of Antigen Processing Machinery Family Genes in Kazakh Primary Esophageal Squamous Cell Carcinoma

  • Sheyhidin, Ilyar (Department of Thoracic Surgery, the First Affliated Hospital, Medical University of Xinjiang) ;
  • Hasim, Ayshamgul (Departments of Pathology, College of Basic Medicine, Medical University of Xinjiang) ;
  • Zheng, Feng (Department of Thoracic Surgery, the First Affliated Hospital, Medical University of Xinjiang) ;
  • Ma, Hong (Departments of Pathology, College of Basic Medicine, Medical University of Xinjiang)
  • Published : 2015.01.06

Abstract

The esophageal squamous cell carcinoma (ESCC) is thought to develop through a multi-stage process. Epigenetic gene silencing constitutes an alternative or complementary mechanism to mutational events in tumorigenesis. Posttranscriptional regulation of human leukocyte antigen class I (HLA-I) and antigen processing machinery (APM) proteins expression may be associated with novel epigenetic modifications in cancer development. In the present study, we determined the expression levels of HLA-I antigen and APM components by immunohistochemistry. Then by a bisulfite-sequencing PCR (BSP) approach, we identified target CpG islands methylated at the gene promoter region of APM family genes in a ESCC cell line (ECa109), and further quantitative analysis of CpG site specific methylation of these genes in cases of Kazakh primary ESCCs with corresponding non-cancerous esophageal tissues using the Sequenom MassARRAY platform. Here we showed that the development of ESCCs was accompanied by partial or total loss of protein expression of HLA-B, TAP2, LMP7, tapasin and ERp57. The results demonstrated that although no statistical significance was found of global target CpG fragment methylation level sof HLA-B, TAP2, tapasin and ERp57 genes between ESCC and corresponding non-cancerous esophageal tissues, there was significant differences in the methylation level of several single sites between the two groups. Of thesse only the global methylation level of LMP7 gene target fragments was statistically higher ($0.0517{\pm}0.0357$) in Kazakh esophageal cancer than in neighboring normal tissues ($0.0380{\pm}0.0214$, p<0.05). Our results suggest that multiple CpG sites, but not methylation of every site leads to down regulation or deletion of gene expression. Only some of them result in genetic transcription, and silencing of HLA-B, ERp57, and LMP7 expression through hypermethylation of the promoters or other mechanisms may contribute to mechanisms of tumor escape from immune surveillance in Kazakh esophageal carcinogenesis.

Keywords

Esophageal squamous cell carcinoma;HLA-I;APM;DNA methylation;mass ARRAY

Acknowledgement

Supported by : Natural Science Fundation

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