Downregulation of tapasin expression in primary human oral squamous cell carcinoma: association with clinical outcome
Downregulation of tapasin expression in primary human oral squamous cell carcinoma: association with clinical outcome
复制标题
原发性人口腔鳞状细胞癌中塔帕辛表达的下调：与临床结果的关联
DOI：
10.1007/s13277-010-0054-4
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发表时间：
2010-10-01
期刊：
影响因子：
--
通讯作者：
Zhang, Zhi-yuan
中科院分区：
文献类型：
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作者：
Jiang, Qian;Pan, Hong-ya;Zhang, Zhi-yuan
肿瘤细胞中经常观察到MHC I类肽负载复合物缺陷，这些缺陷有助于肿瘤细胞逃避免疫监视。Tapasin在内质网MHC I类分子与肽的组装中起重要作用。本研究的目的是探讨tapasin在原发性口腔鳞状细胞癌（OSCC）中的表达及其潜在的临床意义。采用免疫组织化学方法分析67例原发性OSCC患者经福尔马林固定、石蜡包埋的肿瘤活检组织中tapasin的表达情况。采用乙基化特异性聚合酶链反应、硫酸氢基因组测序和表达再激活试验，确定了OSCC细胞系中Tapasin启动子甲基化状态。67例肿瘤中有30例（43%）缺乏tapasin表达，与OSCC病理分化等级差显著相关（P =0.028）。累积5年生存率与病理分化等级（P =0.001）和tapasin表达水平（P =0.015）也有显著相关。tapasin表达降低是生存不良的指标（P =0.048）。在三种OSCC细胞系中均观察到Tapasin启动子甲基化，5-aza-2 ' -脱氧胞苷处理后，Tapasin mRNA和蛋白水平显著升高。tapasin的下调与OSCC患者的不良临床结果相关，可以作为预后生物标志物。启动子甲基化可能导致OSCC中tapasin的下调。
MHC class I peptide loading complex defects are frequently observed in tumor cells which facilitate tumor cells escaping from immune surveillance. Tapasin plays an important role in the assembly of MHC class I molecules with peptides in the endoplasmic reticulum. The aim of this study was to investigate the expression of tapasin in primary oral squamous cell carcinoma (OSCC) and its potential clinical implication. Formalin-fixed, paraffin-embedded tumor biopsies from 67 patients with primary OSCC were analyzed for tapasin expression using immunohistochemistry. Tapasin promoter methylation status in OSCC cell lines was determined using ethylation-specific polymerase chain reaction, bisulphate genomic sequencing, and expression reactivation assay. Lack of tapasin expression was observed in 30 of 67 (43%) tumors and was significantly associated with poor pathologic differentiation grade of OSCC (P =0.028). The cumulative 5-year survival rate was also significantly correlated with pathologic differentiation grade (P =0.001) and tapasin expression level (P =0.015). Decreased tapasin expression was an indicator of poor survival (P =0.048). Tapasin promoter methylation was observed in all three OSCC cell lines examined, and the mRNA and protein levels of tapasin increased markedly after treatment with 5-aza-2′-deoxycytidine. Downregulation of tapasin is associated with a poor clinical outcome for OSCC patients and may serve as a prognostic biomarker. The promoter methylation may contribute to the tapasin downregulation in OSCC.