中国口腔颌面外科杂志 ›› 2023, Vol. 21 ›› Issue (4): 352-359.doi: 10.19438/j.cjoms.2023.04.006

• 论著 • 上一篇    下一篇

MAP7D3在头颈部鳞状细胞癌中的作用探讨

刘雨1,2, 陈羽菱2, 林云涛2, 杨宏宇1,2   

  1. 1.北京大学口腔医学院·口腔医院 综合二科,国家口腔医学中心,国家口腔疾病临床医学研究中心,口腔生物材料和数字诊疗装备国家工程研究中心,北京 100081;
    2.北京大学深圳医院 口腔医学中心 口腔颌面外科,广东省高水平临床重点专科,广东省口腔疾病诊疗技术工程技术研究中心,广东 深圳 518036
  • 收稿日期:2023-02-15 修回日期:2023-04-17 出版日期:2023-07-20 发布日期:2023-08-16
  • 通讯作者: 杨宏宇,E-mail: hyyang192@hotmail.com
  • 作者简介:刘雨(1997-),女,硕士,E-mail: 18237150902@163.com
  • 基金资助:
    深圳市基础研究重点项目(JCYJ20200109140208058)

The role of MAP7D3 in head and neck squamous cell carcinoma

LIU Yu1,2, CHEN Yu-ling2, LIN Yun-tao2, YANG Hong-yu1,2   

  1. 1. Department of General Dentistry II, Peking University School and Hospital of Stomatology; National Center of Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices. Beijing 100081;
    2. Department of Oral and Maxillofacial Surgery, Stomatological Center, Peking University Shenzhen Hospital; Guangdong Provincial High-Level Clinical Key Specialty; Guangdong Province Engineering Research Center of Oral Disease Diagnosis and Treatment. Shenzhen 518036, Guangdong Province, China
  • Received:2023-02-15 Revised:2023-04-17 Online:2023-07-20 Published:2023-08-16

摘要: 目的:利用生物信息学方法探讨MAP7D3在头颈部鳞癌(HNSCC)中的表达水平、诊断及预测预后价值,初步探索MAP7D3表达水平改变对HNSCC细胞系生物学行为的影响。方法:利用生物信息学方法,在HNSCC中对MAP7D3进行表达分析、临床病理特征相关性分析、生存分析、Cox回归分析、ROC曲线分析及基因集富集分析。使用qRT-PCR、免疫组织化学染色法检测MAP7D3在HNSCC细胞系(WSU-HN6、CAL27)及癌组织中的表达。通过转染siRNA敲低MAP7D3的表达,利用qRT-PCR验证MAP7D3的敲低效果,应用CCK-8、流式凋亡实验、划痕实验、Transwell实验检测MAP7D3表达对WSU-HN6和CAL27增殖、凋亡、迁移、侵袭等生物学行为的影响。结果:生物信息学分析、qRT-PCR及免疫组织化学染色表明,在HNSCC中,MAP7D3 mRNA及蛋白质水平均呈高表达。临床相关性分析发现,MAP7D3的表达水平与病理分级相关。与MAP7D3低表达患者相比,MAP7D3高表达患者总体生存期、疾病别生存期及无进展间隔期均更短。单因素及多因素Cox回归分析显示,MAP7D3可作为HNSCC患者预后的独立危险因素。ROC曲线显示,MAP7D3在HNSCC的诊断中具有一定意义。根据GSEA分析结果,MAP7D3高表达组在包括局灶黏附、ECM-受体间相互作用的多条途径中富集。CCK-8、流式凋亡实验、划痕实验及Transwell侵袭实验表明,当MAP7D3表达下调时,细胞增殖、迁移和侵袭能力均受到抑制,细胞凋亡增加。结论:MAP7D3在头颈部鳞癌中高表达,可作为头颈部鳞癌潜在的诊断及预后生物标志物。敲低MAP7D3,能抑制头颈部鳞癌细胞增殖、迁移、侵袭,促进细胞凋亡。

关键词: 头颈部鳞癌, 生物信息学, MAP7D3, 肿瘤标志物

Abstract: PURPOSE: The aim of this study is to figure out MAP7D3 expression level, diagnostic and prognostic value in head and neck squamous cell carcinoma (HNSCC) by bioinformatics technology and to initially explore the effect of the expression change of MAP7D3 on the biological behavior of HNSCC cell lines. METHODS: Expression analysis, clinicopathological characteristics correlation analysis, survival analysis, Cox regression analysis, ROC curve analysis and GSEA analysis were performed in HNSCC by bioinformatics.The expression of MAP7D3 were detected by qRT-PCR and immunohistochemistry staining in HNSCC cell lines(WSU-HN6, CAL27) and HNSCC tissues. Downregulation of MAP7D3 by siRNA was identified by qRT-PCR. CCK8 assay, flow apoptosis assay, wound healing assay and transwell assay ware performed to detect the effect of knocking down MAP7D3 on the biological behaviors of HNSCC cell lines WSU-HN6 and CAL27. RESULTS: MAP7D3 was highly expressed in HNSCC at both RNA and protein level by bioinformatic analysis, qRT-PCR and immunohistochemical staining. Clinical correlation analysis revealed that the expression level of MAP7D3 was correlated with pathological grade. Overall survival, disease specific survival and progress free interval were shorter in patients with high MAP7D3 expression compared with patients with low MAP7D3 expression. Univariate and multivariate Cox regression analysis showed that MAP7D3 expression could be an independent risk factor for prognosis of HNSCC patients. ROC curves showed the diagnostic value of MAP7D3 in differentiating HNSCC tissue from normal tissue. GSEA enrichment analysis showed that MAP7D3 high expression group was enriched in various signaling pathways such as focal adhesion and ECM-receptor interactions. CCK-8 assay, flow apoptosis assay, wound healing assay and transwell assay showed that knockdown of MAP7D3 can inhibit the proliferation, migration, invasion and increase apoptosis of HNSCC cell lines WSU-HN6 and CAL27. CONCLUSIONS: MAP7D3 is highly expressed in HNSCC and can be used as a potential diagnostic and prognostic biomarker for HNSCC. Downregulation of MAP7D3 can inhibit the proliferation, migration and invasion of HNSCC cell and increase cell apoptosis.

Key words: Head and neck squamous cell carcinoma, Bioinformatics, MAP7D3, Tumor biomarkers

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