High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China
High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China
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HLA-DQA1高表达预示中国北方食管鳞状细胞癌患者预后不良
DOI：
10.1097/md.0000000000014454
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发表时间：
2019-02-01
期刊：
影响因子：
1.6
通讯作者：
Zhou, Fu-You
中科院分区：
文献类型：
--
作者：
Shen, Fang-Fang;Pan, Ying;Zhou, Fu-You
背景资料：我们的前期研究表明，主要组织相容性复合体（MHC）与食管鳞状细胞癌（ESCC）的发生发展有关。HLA-DQA 1属于MHC II类家族，可能是食管鳞癌进展的潜在生物标志物。然而，在北方食管癌高发区，HLA-DQA 1与食管癌的相关性尚未得到很好的表征。本研究的目的是探讨HLA-DQA 1表达与食管鳞癌进展及预后的关系。研究方法：我们分析了TCGA数据库中食管癌（EC）样本中HLA-DQA 1的表达谱，并通过免疫组化、蛋白质印迹和定量逆转录聚合酶链反应分别在匹配的EC和正常组织中验证HLA-DQA 1的表达。进一步分析HLA-DQA 1表达与食管鳞癌临床病理特征的关系。测试结果：免疫组化结果显示，食管鳞癌组织中HLA-DQA 1的表达水平明显高于正常食管组织（P <0.001）。食管鳞癌组织中HLA-DQA 1 mRNA和蛋白表达均显著高于正常食管组织。家族史阴性或肿瘤大小>4 cm的患者与较高的HLA-DQA 1表达水平相关。Log-rank法也发现HLA-DQA 1的预后意义，其中HLA-DQA 1的高表达与较短的总生存时间相关。受试者工作特征（ROC）曲线分析得出ROC曲线下面积值为0.693。单因素和多因素分析也提示HLA-DQA 1高表达是食管鳞癌预后不良的潜在指标。结论：我们的研究结果表明，HLA-DQA 1在ESCC的进展中起着重要作用，可能是ESCC诊断和预后的生物标志物，以及ESCC患者治疗的潜在靶点。
Background: Our previous studies demonstrate that the major histocompatibility complex (MHC) is associated with the progression of esophageal squamous cell carcinoma (ESCC). HLA-DQA1, which belongs to the MHC Class II family, may be a potential biomarker in ESCC progression. However, the association between HLA-DQA1 and ESCC in high-incidence area of northern China has not been well characterized. The purpose of this study is to investigate the relationship of HLA-DQA1 expression with the progression and prognosis of ESCC. Methods: We analyzed the expression profiles of HLA-DQA1 in esophageal cancer (EC) samples in the TCGA database and validated HLA-DQA1 expression by immunohistochemistry, western blotting, and quantitative reverse-transcription polymerase chain reaction in matched EC and normal tissues, respectively. The correlation between HLA-DQA1 expression and clinicopathologic characteristics of ESCC was further analyzed. Result: Immunohistochemical analysis indicated that the expression level of HLA-DQA1 in ESCC tissues was significantly higher than the matched normal tissues (P < .001). HLA-DQA1 mRNA and protein expression were significantly higher in ESCC tissues compared to the matched normal tissues. Patients with family history negative or with tumor sizes >4 cm were associated with higher HLA-DQA1 expression levels. A prognostic significance of HLA-DQA1 was also found by the Log-rank method, in which high expression of HLA-DQA1 was correlated with a shorter overall survival time. The receiver operating characteristic (ROC) curve analysis yielded the area under the ROC curve value of 0.693. Univariate and multivariate analyses also suggest that high expression of HLA-DQA1 is a potential indicator for poor prognosis of ESCC. Conclusions: Our results demonstrate that HLA-DQA1 plays an important role in ESCC progression and may be a biomarker for ESCC diagnosis and prognosis, as well as a potential target for the treatment of patients with ESCC.