Shen Fang-Fang, Pan Ying, Li Jing-Zhong, Zhao Fang, Yang Hai-Jun, Li Jun-Kuo, Gao Zhao-Wei, Su Jing-Fen, Duan Li-Juan, Lun Shu-Min, Zhang Peng, Tian Lin-Qiang, Sun Gang, Huang Da, Cao Yan-Tian, Zhou Fu-You
The Key Laboratory for Tumor Translational Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang.
Anyang Key Laboratory for Esophageal Cancer Research, Anyang Tumor Hospital, Anyang.
Medicine (Baltimore). 2019 Feb;98(8):e14454. doi: 10.1097/MD.0000000000014454.
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.
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.
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.
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.
我们之前的研究表明,主要组织相容性复合体(MHC)与食管鳞状细胞癌(ESCC)的进展相关。属于MHC II类家族的HLA - DQA1可能是ESCC进展中的一个潜在生物标志物。然而,在中国北方高发地区,HLA - DQA1与ESCC之间的关联尚未得到充分阐明。本研究的目的是探讨HLA - DQA1表达与ESCC进展及预后的关系。
我们分析了TCGA数据库中食管癌(EC)样本的HLA - DQA1表达谱,并分别通过免疫组织化学、蛋白质印迹法和定量逆转录聚合酶链反应在配对的EC组织和正常组织中验证HLA - DQA1的表达。进一步分析HLA - DQA1表达与ESCC临床病理特征之间的相关性。
免疫组织化学分析表明,ESCC组织中HLA - DQA1的表达水平显著高于配对的正常组织(P < 0.001)。与配对的正常组织相比,ESCC组织中HLA - DQA1的mRNA和蛋白质表达显著更高。家族史阴性或肿瘤大小>4 cm的患者与较高的HLA - DQA1表达水平相关。通过对数秩检验方法也发现了HLA - DQA1的预后意义,其中HLA - DQA1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还表明,HLA - DQA1的高表达是ESCC预后不良的一个潜在指标。
我们的结果表明,HLA - DQA1在ESCC进展中起重要作用,可能是ESCC诊断和预后的生物标志物,也是ESCC患者治疗的潜在靶点。