背景:头颈部鳞状细胞癌是一种高发病率和死亡率的恶性肿瘤。MMP家族在肿瘤的侵袭和转移中起着重要的作用。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.
方法:Oncomine,UALCAN,GEPIA,cBioportal,遗传狂躁症,STRING,DAVID6.8,TRRUST,TIMER和Linkedomics用于分析。
结果:HNSC中MMP1,MMP3,ILF3,MMP7,MMP9,MMP10,MMP11,MMP12,MMP13和MMP16的mRNA表达水平高于正常组织,而MMP15的mRNA表达水平降低。HNSC组织中MMP1和MMP14的相对表达水平最高。发现MMP3,MMP11,MMP25的表达与HNSC患者的病理分期之间存在显着相关性。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家族成员都有遗传变化,其中大部分是放大和深度损失。在分析邻居基因网络和蛋白质相互作用时,我们发现MMP家族与25个相邻基因相互作用,除ILF3、MMP19、MMP20、MMP21、MMP23B、MMP27和MMP28,其他MMP蛋白相互作用。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家族中两个最常见的激酶靶标.我们还发现MMP家族的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患者的临床结果显著相关。
结论:MMP家族可能作为HNSC的治疗靶点和预后标志物。
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.