口腔医学研究

口腔医学研究 ›› 2019, Vol. 35 ›› Issue (11): 1044-1047.DOI: 10.13701/j.cnki.kqyxyj.2019.11.009

• 口腔颌面外科学研究 • 上一篇    下一篇

DNA损伤诱导转录子4基因在口腔鳞状细胞癌中的表达及临床意义

戈春城1, 汪羽1*, 何三纲2, 徐佳1, 王曦1, 童国勇1, 余周庆1   

  1. 1. 湖北省恩施土家族苗族自治州中心医院口腔诊疗中心 湖北 恩施 445000;
    2. 武汉大学口腔医院口腔颌面创伤与整形外科 湖北 武汉 430079
  • 收稿日期:2019-05-12 出版日期:2019-11-28 发布日期:2019-11-21
  • 通讯作者: 汪羽,E-mail:4099030@qq.com
  • 作者简介:戈春城(1974~ ),男,湖北武汉人,学士,主任医 师,研究方向为口腔肿瘤的防治。

Expression and Clinical Significance of DDIT4 Gene in Oral Squamous Cell Carcinoma

GE Chuncheng1, WANG Yu1*, HE Sangang2, XU Jia1, Wang Xi1, TONG Guoyong1, YU Zhouqing1   

  1. 1. Oral Diagnosis and Treatment Center, Enshi Tujia and Miao Autonomous Prefecture Center Hospital, Enshi 445000, China;
    2. Department of Oral and Maxillofacial Trauma and Plastic Surgery, Stomatology Hospital, Wuhan University, Wuhan 430079, China
  • Received:2019-05-12 Online:2019-11-28 Published:2019-11-21

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摘要： 目的: 探讨DNA损伤诱导转录子4(DNA damage inducible transcript 4,DDIT4)基因在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达水平及其临床意义。方法: 分别下载癌症和肿瘤基因图谱(The Cancer Genome Atlas,TCGA)数据库中的OSCC队列数据(n=362)及基因表达综合(Gene Expression Omnibus,GEO)数据库中的GSE42743数据集(n=103)。比较OSCC组和正常对照组中DDIT4的表达水平,并分析DDIT4与OSCC患者临床特征和预后的关系。此外,利用生物信息学方法寻找DDIT4可能参与的生物学功能。结果: DDIT4在OSCC组中的表达水平高于对照组,差异有统计学意义(P<0.001)。在OSCC患者中,DDIT4的表达水平与肿瘤分期呈正相关(P<0.001),且OSCC高表达组的总生存率明显低于低表达组(Log-rank检验,P<0.01)。进一步行Cox回归分析,结果提示DDIT4高表达是OSCC患者预后不良的独立预测因素(P<0.05)。生物信息学分析表明,DDIT可能与低氧反应、糖酵解、雷帕霉素靶蛋白C1(mammalian target of rapamycin C1,mTORC1)信号通路、核因子-κB(nuclear factor kappa-B,NF-κB)介导的肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)信号通路、G2M检查点、p53信号通路等生物学功能有关。结论: DDIT4基因在OSCC患者中呈高表达状态,并且其表达水平与肿瘤分期有关。高表达DDIT4基因的OSCC患者预后不佳。因此,DDIT4可作为OSCC预后评估的一种标记物。

关键词: 口腔鳞状细胞癌, DNA损伤诱导转录子4, 预后, 生物标志物

Abstract: Objective: To explore the expression and clinical significance of DDIT4 gene in oral squamous cell carcinoma (OSCC). Methods: The OSCC cohort data from TCGA database and GSE42743 dataset from GEO database were downloaded. DDIT4 expression in OSCC group and normal control group were compared, and the association of DDIT4 with clinical data and prognosis were analyzed. Moreover, bioinformatics analysis was used to identify the potential biological functions associated with DDIT4. Results: The expression of DDIT4 was higher in OSCC than in control groups, with statistical significance between groups (P<0.001). In patients with OSCC, DDIT4 expression was positively correlated with tumor stage (P<0.001), and the survival rate of high DDIT4 group was significantly higher than that of low DDIT4 group (Log-rank P<0.01). Additional, Cox regression analysis indicated that high expression of DDIT4 was an independent predictor for poor prognosis of OSCC patients (P<0.05). Bioinformatics analysis showed that DDIT4 may be associated with hypoxia, glycolysis, mTORC1 signaling, TNF-α signaling via NF-κb, G2M checkpoint, and p53 pathway. Conclusion: DDIT4 expression is increased in OSCC patients, which is associated with the tumor stage. OSCC patients with high DDIT4 have a poor prognosis. Therefore, DDIT4 is a potential biomarker for prognostic evaluation of GC.

Key words: oral squamous cell carcinoma, DNA damage inducible transcript 4, prognosis, biomarker