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去甲基化介导的黑色素瘤相关抗原 A11 的上调与食管鳞状细胞癌的恶性进展相关。

Demethylation-mediated upregulation of melanoma-associated antigen-A11 correlates with malignant progression of esophageal squamous cell carcinoma.

机构信息

Department of Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

Department of Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China; Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.

出版信息

Dig Liver Dis. 2019 Oct;51(10):1475-1482. doi: 10.1016/j.dld.2019.04.018. Epub 2019 May 31.

DOI:10.1016/j.dld.2019.04.018
PMID:31155488
Abstract

BACKGROUND

The expression and methylation status of oncogenes are closely related to the onset and progression of cancer.

AIMS

To explore the role and methylation status of melanoma-associated antigen-A11 in the pathogenesis of esophageal squamous cell carcinoma.

METHODS

116 esophageal squamous cell carcinoma patients with tumor tissues and corresponding adjacent normal tissues were obtained. The expression level and methylation status of melanoma-associated antigen-A11 in esophageal cancer cell lines and esophageal squamous cell carcinoma tissues were determined respectively.

RESULTS

Significant up-regulation of melanoma-associated antigen-A11 was detected in esophageal cancer cell lines and esophageal squamous cell carcinoma tissues. Up-regulation of melanoma-associated antigen-A11 contributed to proliferation and invasion in cancer cells. Hypomethylation of the CpG site was associated with pathological differentiation, clinical stage, tumor size, lymph node metastasis and distant metastasis. Esophageal squamous cell carcinoma patients in stage III and IV, with high expression of melanoma-associated antigen-A11 or hypomethylation of the CpG site within the promoter demonstrated poor survival.

CONCLUSION

Melanoma-associated antigen-A11 is up-regulated in esophageal squamous cell carcinoma at least partly by hypomethylation of the CpG site within the promoter and this hypomethylation may affect the prognosis of esophageal squamous cell carcinoma patients.

摘要

背景

癌基因的表达和甲基化状态与癌症的发生和进展密切相关。

目的

探讨黑色素瘤相关抗原-A11 在食管鳞状细胞癌发病机制中的作用和甲基化状态。

方法

收集 116 例食管鳞状细胞癌患者的肿瘤组织及相应的癌旁正常组织,分别检测食管癌细胞系和食管鳞状细胞癌组织中黑色素瘤相关抗原-A11 的表达水平和甲基化状态。

结果

黑色素瘤相关抗原-A11 在食管癌细胞系和食管鳞状细胞癌组织中均呈显著上调。黑色素瘤相关抗原-A11 的上调促进了癌细胞的增殖和侵袭。CpG 位点的低甲基化与病理分化、临床分期、肿瘤大小、淋巴结转移和远处转移有关。III 期和 IV 期的食管鳞状细胞癌患者,黑色素瘤相关抗原-A11 表达水平高或启动子内 CpG 位点低甲基化的患者生存状况较差。

结论

黑色素瘤相关抗原-A11 在食管鳞状细胞癌中至少部分通过启动子内 CpG 位点的低甲基化而上调,这种低甲基化可能影响食管鳞状细胞癌患者的预后。

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