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[摘要]
目的:探讨食管鳞状细胞癌 (esophageal squamous cell cancer, ESCC) 患者的食管鳞癌组织、癌旁组织中 Bin1 基因启动子甲基化状态及其mRNA的表达及其临床意义。方法:采用实时荧光定量PCR(qRT-PCR)分别检测58例经病理证实的ESCC患者的食管鳞癌组织、癌旁组织中Bin1 基因mRNA的表达情况;用甲基化特异性PCR(MSP)检测上述食管鳞癌组织中 Bin1 基因启动子甲基化状态,比较ESCC患者Bin1甲基化状态与临床病理分期的关系。结果: ESCC组织中 Bin1基因启动子甲基化率明显高于癌旁组织(58.62% vs 25.86%, χ2=12.76, P<0.01),Bin1甲基化状态与患者TNM分期、肿瘤侵润深度、分化程度、淋巴结转移相关(均P<0.05)。ESCC组织中 Bin1mRNA的表达水平明显低于癌旁组织\[(0.78±0.05) vs (1.03±0.03), t=9.643, P<0.01)\];发生Bin1甲基化的组织中Bin1 mRNA表达水平明显低于未发生甲基化的组织\[(0.68±0.04) vs (0.85±0.07), t=2.476, P<0.05\]。结论:Bin1基因启动子区甲基化状态可能与ESCC的发生密切相关,它是ESCC中 Bin1mRNA低表达或缺失的机制之一,且与ESCC进展和淋巴结转移有关。
[Key word]
[Abstract]
Objective:To detect the methylation status of Bin1 gene promoter and its mRNA expression in cancer tissues and para-carcinoma normal tissues from patients with esophageal squamous cell cancer (ESCC), and to explore its clinical significance. Methods: The expression level of Bin1 mRNA and its methylation status in ESCC tissues and the corresponding para-carcinoma normal tissues from 58 patients were determined by real-time quantitative RT-PCR (qRT-PCR) and methylation specific PCR (MSP). The relationship between Bin1 methylation status and clinical pathological staging was compared. Results: The methylation frequency of Bin1 in ESCC tissues was significantly higher than that in the corresponding para-carcinoma normal tissues (58.62% vs 25.86%, P<0.01), and the Bin1 methylation status was closely correlated with TNM stage, tumor invasion depth, tumor differentiation and lymph node metastasis (all P<0.05). Compared with para-carcinoma tissue specimens, the expression of Bin1mRNA in ESCC tissues was significantly lower (\[0.78±0.05\] vs \[1.03±0.03\], t=9.643, P<0.01) . The expression of Bin1 mRNA in ESCC tissues with methylation was significantly lower than that in ESCC tissues without methylation (\[0.68±0.04\] vs \[0.85±0.07\], t=2476, P<0.05). Conclusion: Aberrant promoter methylation of Bin1 might be closely related to the development of ESCC, and it is one of the possible mechanisms that leads low expression or deletion of Bin1 in ESCC. The DNA methylation of Bin1 might be closely associated with tumor invasion and lymph node metastasis of ESCC.
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[基金项目]
国家自然科学基金资助项目(No.81201607);河北省杰出青年基金资助项目(No.H2014206320);河北省高层次人才资助项目(No.A201401040)