Head and Neck Squamous Cell Carcinoma is a malignant tumor with high morbidity and mortality. The MMP family plays an important role in tumor invasion and metastasis. However, the mechanistic value of the MMP family as a therapeutic target and prognostic biomarker in HNSC has not been fully elucidated. Oncomine, UALCAN, GEPIA, cBioportal, GeneMANIA, STRING, DAVID6.8, TRRUST, TIMER and Linkedomics were used for analysis. The mRNA expression levels of MMP1, MMP3, ILF3, MMP7, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16 were higher in HNSC than those in normal tissues, while the mRNA expression level of MMP15 was reduced. The relative expression levels of MMP1 and MMP14 were the highest in HNSC tissues. A significant correlation was found between the expression of MMP3, MMP11, MMP25 and the pathological stage of HNSC patients. There was no significant associations between all the MMP family members expression levels and DFS. Increased mRNA levels of MMP1, MMP8 and MMP25 were significantly associated with OS. In addition, we investigated the genetic changes of the MMP family in HNSC and found that all the MMP family members had genetic changes, most of which were amplification and depth loss. In the analysis of neighbor gene network and protein interaction, we found that the MMP family interacted with 25 neighboring genes, except for ILF3, MMP19, MMP20, MMP21, MMP23B, MMP27 and MMP28, other MMP proteins interacted with each other. Functional enrichment analysis showed that the MMP family could be present in the extracellular matrix, regulate peptidase activity, and participate in the catabolism of collagen. Meanwhile, we identified the transcription factor targets and kinase targets of the MMP family and found that ATM and ATR were the two most common kinase targets in the MMP family. We also found a significant correlation between the MMP family expression and immune cell infiltration. Cox proportional risk model analysis showed that macrophages, MMP14, MMP16, and MMP19 were significantly associated with clinical outcomes in HNSC patients. The MMP family might serve as therapeutic target and prognostic biomarker in HNSC.

中文翻译：

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鉴定 MMP 家族作为头颈部鳞状细胞癌微环境中的治疗靶点和预后生物标志物

头颈部鳞状细胞癌是一种发病率和死亡率都很高的恶性肿瘤。MMP家族在肿瘤侵袭和转移中起重要作用。然而，MMP 家族作为 HNSC 治疗靶点和预后生物标志物的机制价值尚未完全阐明。使用 Oncomine、UALCAN、GEPIA、cBioportal、GeneMANIA、STRING、DAVID6.8、TRRUST、TIMER 和 Linkedomics 进行分析。MMP1、MMP3、ILF3、MMP7、MMP9、MMP10、MMP11、MMP12、MMP13和MMP16的mRNA表达水平在HNSC中高于正常组织，而MMP15的mRNA表达水平降低。MMP1和MMP14的相对表达水平在HNSC组织中最高。MMP3、MMP11、MMP25的表达与HNSC患者的病理分期存在显着相关性。所有 MMP 家族成员的表达水平与 DFS 之间没有显着关联。MMP1、MMP8 和 MMP25 的 mRNA 水平升高与 OS 显着相关。此外，我们调查了HNSC中MMP家族的遗传变化，发现所有MMP家族成员都发生了遗传变化，其中大部分是扩增和深度缺失。在邻居基因网络和蛋白质相互作用分析中，我们发现MMP家族与25个邻居基因相互作用，除ILF3、MMP19、MMP20、MMP21、MMP23B、MMP27和MMP28外，其他MMP蛋白之间存在相互作用。功能富集分析表明，MMP家族可存在于细胞外基质中，调节肽酶活性，参与胶原蛋白的分解代谢。同时，我们确定了 MMP 家族的转录因子靶标和激酶靶标，发现 ATM 和 ATR 是 MMP 家族中最常见的两个激酶靶标。我们还发现 MMP 家族表达与免疫细胞浸润之间存在显着相关性。Cox 比例风险模型分析表明，巨噬细胞、MMP14、MMP16 和 MMP19 与 HNSC 患者的临床结果显着相关。MMP 家族可能作为 HNSC 的治疗靶点和预后生物标志物。和 MMP19 与 HNSC 患者的临床结果显着相关。MMP 家族可能作为 HNSC 的治疗靶点和预后生物标志物。和 MMP19 与 HNSC 患者的临床结果显着相关。MMP 家族可能作为 HNSC 的治疗靶点和预后生物标志物。