基质金属蛋白酶9/11在口腔鳞癌诊断及治疗中的应用价值-现代医学

基质金属蛋白酶9/11在口腔鳞癌诊断及治疗中的应用价值

单位：1. 东南大学附属中大医院口腔科, 江苏南京 210048;
2. 福建医科大学附属第一医院口腔颌面外科, 福建福州 350004

分类号：R739.8

出版年·卷·期（页码）：2023·51·第二期（202-210）

摘要：

目的：探讨基质金属蛋白酶9/11（MMP9/11）在口腔鳞状细胞癌中的表达及其临床应用价值。方法：利用R语言在癌症基因组图谱（TCGA）数据库中分析MMP9/11在泛癌和口腔鳞癌中的表达，分析MMP9/11在口腔鳞癌中ROC曲线、共表达基因及其功能，以及MMP9/11的表达与免疫细胞浸润的相关性；收集临床样本利用实时荧光定量聚合酶链反应（RT-PCR）法检测口腔鳞癌及癌旁组织中MMP9/11的mRNA水平的表达，并分析MMP9/11表达对各临床特征因素的影响。结果：MMP9/11在口腔鳞癌及大多数癌症中高表达，临床标本中癌组织的MMP9/11表达高于癌旁组织（P<0.001）且这种高表达影响肿瘤细胞的淋巴转移和肿瘤大小（P<0.05）；ROC曲线分析显示，MMP9的曲线下面积（AUC）为0.949（95%CI 0.916~0.982），MMP11的AUC为0.962（95%CI 0.936~0.987）；共表达基因分析显示，与MMP9正相关的基因有9 063个，负相关的基因872个，与MMP11正相关的基因有10 909个，负相关的基因633个，且经GO-KEGG富集分析共表达基因主要涉及细胞外基质（ECM）结构成分及含有ECM胶原蛋白的细胞成分，并参与蛋白的消化与吸收和ECM受体的相互作用等信号通路；免疫细胞浸润分析发现，MMP9的表达与多种免疫细胞呈正相关，如中性粒细胞、树突状细胞、细胞毒性细胞等，而MMP11的表达与树突状细胞呈正相关。结论：MMP9/11在口腔鳞癌的诊断及治疗中具有潜在的应用价值。

Objective: To investigate the expression of matrix metalloproteinase 9/11(MMP9/11) in oral squamous cell carcinoma and its clinical application value. Methods: The expressions of MMP9/11 in pan-cancer and oral squamous cell carcinoma were analyzed using R language in the cancer genome atlas(TCGA) database. Meanwhile, ROC curve, co-expressed genes and functions of MMP9/11 in oral squamous cell carcinoma were analyzed, and the correlation between MMP9/11 expression and immune cell infiltration was also studied. Clinical samples were collected and the mRNA expression of MMP9/11 in cancer tissues and adjacent tissues was detected by RT-PCR. The effect of MMP9/11 expression on clinical characteristics was analyzed at the same time. Results: MMP9/11 were overexpressed in oral squamous cell carcinoma and most cancers. RT-PCR results showed that the expression of MMP9/11 in cancer tissues was higher than that in adjacent tissues(P<0.001), which affected lymphatic metastasis and tumor size(P<0.05). ROC curve analysis showed that the area under curve(AUC) of MMP9 was 0.949(95%CI 0.916-0.982), and that of MMP11 was 0.962(95%CI 0.936-0.987). Co-expression gene analysis showed that 9 063 genes were positively correlated with MMP9, and 872 were negatively correlated with MMP9, and that there were 10 909 genes positively correlated and 633 negatively correlated with MMP11. GO-KEGG enrichment analysis showed that the co-expressed genes were mainly involved in the structural components of extracellular matrix(ECM) and the cellular components containing ECM collagen, and were involved in protein digestion and absorption, ECM receptor interaction and other signaling pathways. Immune cell infiltration analysis revealed that the expression of MMP9 was positively correlated with a variety of immune cells, such as neutrophils, dendritic cells, cytotoxic cells, etc., and the expression of MMP11 was positively correlated with dendritic cells. Conclusion: MMP9/11 have potential application value in the diagnosis and treatment of oral squamous cell carcinoma.

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