Department of Periodontics & Oral Mucosal Diseases, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, Luzhou, Sichuan, China.
J Transl Med. 2023 Mar 20;21(1):208. doi: 10.1186/s12967-023-04052-3.
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.
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 家族在肿瘤的侵袭和转移中起着重要作用。然而，MMP 家族作为 HNSC 的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。
与正常组织相比，MMP1、MMP3、ILF3、MMP7、MMP9、MMP10、MMP11、MMP12、MMP13 和 MMP16 在 HNSC 中的 mRNA 表达水平更高，而 MMP15 的 mRNA 表达水平降低。在 HNSC 组织中，MMP1 和 MMP14 的相对表达水平最高。MMP3、MMP11 和 MMP25 的表达与 HNSC 患者的病理分期呈显著相关。所有 MMP 家族成员的表达水平与 DFS 之间无显著相关性。MMP1、MMP8 和 MMP25 的 mRNA 水平升高与 OS 显著相关。此外，我们研究了 HNSC 中 MMP 家族的遗传变化，发现所有 MMP 家族成员均发生遗传改变，其中大部分为扩增和深度缺失。在邻近基因网络和蛋白质相互作用的分析中，我们发现 MMP 家族与 25 个邻近基因相互作用，除了 ILF3、MMP19、MMP20、MMP21、MMP23B、MMP27 和 MMP28 之外，其他 MMP 蛋白之间也相互作用。功能富集分析表明，MMP 家族可以存在于细胞外基质中，调节肽酶活性，并参与胶原蛋白的分解代谢。同时，我们鉴定了 MMP 家族的转录因子靶标和激酶靶标，发现 ATM 和 ATR 是 MMP 家族中最常见的两种激酶靶标。我们还发现 MMP 家族的表达与免疫细胞浸润之间存在显著相关性。Cox 比例风险模型分析表明，巨噬细胞、MMP14、MMP16 和 MMP19 与 HNSC 患者的临床结局显著相关。
MMP 家族可能作为 HNSC 的治疗靶点和预后生物标志物。
