MMP25 Regulates Immune Infiltration Level and Survival Outcome in Head and Neck Cancer Patients
MMP25 Regulates Immune Infiltration Level and Survival Outcome in Head and Neck Cancer Patients
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MMP25 调节头颈癌患者的免疫浸润水平和生存结果
DOI：
10.3389/fonc.2020.01088
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发表时间：
2020-07-29
影响因子：
4.7
通讯作者：
Liao, Guiqing
中科院分区：
文献类型：
--
作者：
Liang, Yujie;Guan, Chenyu;Liao, Guiqing
研究背景：基质金属蛋白酶25（MMP 25）是基质金属蛋白酶（MMP）的关键基因。然而，MMP 25在头颈部肿瘤发病中的分子机制仍不清楚。研究方法：使用癌症基因组图谱（TCGA）数据库分析MMP 25表达，并使用Kaplan-Meier和考克斯回归分析其对临床预后的影响。采用CIBERSORT、TIMER、ESTIMATE等方法检测MMP 25与免疫浸润的相关性。此外，通过基因集富集分析（GSEA）、基因本体（GO）和加权基因共表达网络分析（WGCNA）分析MMP 25表达与分子机制之间的关系。结果如下：MMP 25表达水平与头颈部肿瘤的预后和免疫浸润水平相关，尤其是与活化的CD 4+记忆T细胞相关。此外，MMP 25表达可能介导基因，例如IRF 8、IKZF 1和DOCK 2，以及肿瘤相关途径，包括p53信号传导、PI 3 K/AKT/mTOR信号传导和JAK/STAT信号传导途径。结论：MMP 25在头颈部恶性肿瘤的免疫浸润水平及预后中起重要作用。此外，MMP 25的表达与多种癌基因和肿瘤相关通路的调节显著相关。
Background: MMP25 is a critical gene of matrix metalloproteinases (MMPs). However, the molecular mechanism of MMP25 in head and neck cancer pathogenesis remains unclear. Methods: MMP25 expression was analyzed using The Cancer Genome Atlas (TCGA) database, and its influence on clinical prognosis was performed using Kaplan–Meier and Cox regression analyses. The correlation between MMP25 and immune infiltration was investigated by CIBERSORT, TIMER, and ESTIMATE. In addition, the relationship between MMP25 expression and molecular mechanisms was analyzed by gene set enrichment analysis (GSEA), gene ontology (GO), and weighted gene co-expression network analysis (WGCNA). Results: MMP25 expression level correlated with prognosis and immune infiltrating levels, especially activated CD4+ memory T cells, in head and neck cancer. Moreover, MMP25 expression potentially mediated genes, such as IRF8, IKZF1, and DOCK2, and tumor-associated pathways, including p53 signaling, PI3K/AKT/mTOR signaling, and JAK/STAT signaling pathway. Conclusions: These findings suggested that MMP25 plays a critical role in the prognosis and immune infiltration level of head and neck cancer. In addition, MMP25 expression significantly correlated with the regulation of various oncogenes and tumor-related pathways.