- Volume 15 Issue 23
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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
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 (
Esophageal squamous cell carcinoma;HLA-I;APM;DNA methylation;mass ARRAY
Supported by : Natural Science Fundation
- Akash M, Mehta Ekaterina S, Jordanova G G, Kenter S F, Gert-Jan F (2008). Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma. Cancer Immunol Immunother, 57, 197-206.
- Ayshamgul H, Ma H, Ilyar S, Zhang LW, Abulizi A (2011). Association of defective HLA-I expression with antigen processing machinery and their association with clinicopathological characteristics in Kazak patients with esophageal cancer. Chin Med J (Engl), 124, 341-6.
- Barbara Seliger (2012) Novel insights into the molecular mechanisms of HLA class I abnormalities. Cancer Immunol Immunother, 61, 249-54. https://doi.org/10.1007/s00262-011-1153-9
- Cabrera CM, Jimenez P, Cabrera T, et al (2003). Total loss of MHC class I in colorectal tumors can be explained by two molecular pathways: beta2-microglobulin inactivation in MSI-positive tumors and LMP7/TAP2 downregulation in MSI-negative tumors. Tissue Antigens, 61, 211-9. https://doi.org/10.1034/j.1399-0039.2003.00020.x
- Campoli M, Ferrone S (2008). HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene, 27, 5869-85. https://doi.org/10.1038/onc.2008.273
- Chang CC, Ogino T, Mullins DW, et al (2006). Defective human leukocyte antigen class I-associated antigen presentation caused by a novel beta2-microglobulin loss-of-function in melanoma cells. J Biol Chem, 281, 18763-73. https://doi.org/10.1074/jbc.M511525200
- D'Alessio AC, Szyf M: Epigenetic tete-a-tete (2006). The bilateral relationship between chromatin modifications and DNA methylation. Biochem Cell Biol, 84, 463-76. https://doi.org/10.1139/o06-090
- Garrido C, Algarra I, Maleno I, et al (2010). Alterations of HLA class I expression in human melanoma xenografts in immunodeficient mice occur frequently and are associated with higher tumorigenicity. Cancer Immunol Immunother, 59, 13-26. https://doi.org/10.1007/s00262-009-0716-5
- Garrido F, Algarra I, Garcia-Lora AM (2010). The escape of cancer from T lymphocytes: immunoselection of MHC class I loss variants harboring structural-irreversible ''hard'' lesions. Cancer Immunol Immunother, 59, 1601-6. https://doi.org/10.1007/s00262-010-0893-2
- Griffioen M, Ouwerkerk IJ, Harten V, Schrier PI (1999). HLA-B down-regulation in human melanoma is mediated by sequences located downstream of the transcription-initiation site. Int J Cancer, 80, 573-80. https://doi.org/10.1002/(SICI)1097-0215(19990209)80:4<573::AID-IJC15>3.0.CO;2-S
- Helen P, Cathro Mark E, Smolkin D, et al (2010). Relationship between HLA class I antigen processing machinery component expression and the clinico- pathologic characteristics of bladder carcinomas. Cancer Immunol Immunother, 59, 465-72. https://doi.org/10.1007/s00262-009-0765-9
- Ingrid C, Cristina B, Eleonora M, et al (2011). Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues. BMC Cancer, 11, 244. https://doi.org/10.1186/1471-2407-11-244
- Jemal A, Siegel R, Xu JQ, et al (2010). Cancer statistics, Ca Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
- Jensen PE (2007). Recent advances in antigen processing and presentation. Nat Immunol, 8, 1041-8. https://doi.org/10.1038/ni1516
- Kleinberg L, Forastiere AA (2007). Chemoradiation in the management of esophageal cancer. J Clin Oncol, 25, 4110-7. https://doi.org/10.1200/JCO.2007.12.0881
- Laura Menendez, L DeEtte Walker, et al (2008) Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors. Molecular Cancer, 7, 43. https://doi.org/10.1186/1476-4598-7-43
- Liu Q, Hao C, Su P, Shi J (2009). Down-regulation of HLA class I antigen-processing machinery components in esophageal squamous cell carcinomas: association with disease progression. Scand J Gastroenterol, 44, 960-9. https://doi.org/10.1080/00365520902998679
- Manning J, Indrova M, Lubyova B, et al (2008). Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours. Immunology, 123, 218-27.
- N Yamada, Y Nishida, H Tsutsumida, et al (2009). Promoter CpG methylation in cancer cells contributes to the regulation of MUC4. Br J Cancer, 100, 344-51. https://doi.org/10.1038/sj.bjc.6604845
- Nie Y, YangG-Y, SongY, et al (2001). DNA hypermethylation is a mechanism for loss of expression of the HLA class I genes in human esophageal squamous cell carcinomas. Carcinogenesis, 22, 1615-23. https://doi.org/10.1093/carcin/22.10.1615
- Raghavan M, Del Cid N, Rizvi SM, Peters LR (2008). MHC class I assembly: out and about. Trends Immunol, 29, 436-43. https://doi.org/10.1016/j.it.2008.06.004
- Sarah BU, David EF (2008). Esophageal cancer: epidemiology, pathogenesis and prevention. Nat Clin Pract, 5, 517-26.
- Seliger B (2008). Molecular mechanisms of MHC class I abnormalities and APM components in human tumors. cancer immunol. Immunother, 57, 1719-26 https://doi.org/10.1007/s00262-008-0515-4
- Sers C, Kuner R, Falk CS, et al (2009). Down-regulation of HLA Class I and NKG2D ligands through a concerted action of MAPK and DNA methyltransferases in colorectal cancer cells. Int J Cancer, 125, 1626-39. https://doi.org/10.1002/ijc.24557
- Sugimura T, Ushijima T (2000). Genetic and epigenetic alterations in carcinogenesis. Mutat Res, 462, 235-46. https://doi.org/10.1016/S1383-5742(00)00005-3
- Tomasi TB, Magner WJ, Khan AN (2006). Epigenetic regulation of immune escape genes in cancer. Cancer Immunol Immunother, 10, 1159-84.
- Yamada N, Nishida Y, Tsutsumida H, Hamada T, Goto M, Higashi M, Nomoto M, Yonezawa S (2008) MUC1 expression is regulated by DNA methylation and histone H3 lysine 9 modification in cancer cells. Cancer Res, 68, 2708-16. https://doi.org/10.1158/0008-5472.CAN-07-6844
- Yan Nie, Jie Liao, Xin Zhao, et al (2002). Detection of multiple gene hypermethylation in the development of esophageal squamous cell carcinoma. Carcinogenesis, 23, 1713-20. 1713-20. https://doi.org/10.1093/carcin/23.10.1713
- Ye Q, Shen Y, Wang X, et al (2009). Hypermethylation of HLA class I gene is associated with HLA class I down-regulation in human gastric cancer. Tissue Antigens, 75, 30-9.
- Zhang Y (1988). The distribution of esophageal cancer in Xinjiang. Xinjiang Yixueyuan Xuebao, 11, 139-44.
- Zheng S, Vuitton L, Sheyhidin I, et al (2010). Northwestern China: a place to learn more on oesophageal cancer. Part one: behaviour and environmental risk factors. Eur J Gastroenterol Hepatol, 22, 917-25. https://doi.org/10.1097/MEG.0b013e3283313d8b
- HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma vol.113, pp.6, 2015, https://doi.org/10.1038/bjc.2015.297
- Multiple Structural and Epigenetic Defects in the Human Leukocyte Antigen Class I Antigen Presentation Pathway in a Recurrent Metastatic Melanoma Following Immunotherapy vol.290, pp.44, 2015, https://doi.org/10.1074/jbc.M115.676130
- Association between protocadherin 8 promoter hypermethylation and the pathological status of prostate cancer vol.14, pp.2, 2017, https://doi.org/10.3892/ol.2017.6282