Association between the expression of MMP1 gene and prognosis in head and neck squamous cell carcinoma
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摘要: 目的:研究MMP1基因表达水平在头颈部鳞状细胞癌(HNSCC)患者中的表达情况及预后相关性,并探究可能的作用机制。方法:在TCGA公共数据库中下载HNSCC的RNA测序数据及相关临床数据,对样本中的MMP1基因表达数据及其对应的临床信息进行回顾性分析;采用数据库基因芯片数据验证MMP1基因与HNSCC发生的相关性;生存分析MMP1与HNSCC患者预后指标(无病生存期与总生存期)的关系;采用基因集富集分析方法探讨MMP1基因在HNSCC中可能的作用机制。结果:332例HNSCC患者RNA测序样本中,MMP1基因表达与淋巴管浸润、肿瘤分级明显相关(P<0.01),表达越高,患者越易发生淋巴结转移,恶性程度越高;数据库基因芯片数据证实HNSCC组织中MMP1表达水平明显高于正常黏膜组织(t=12.622,P<0.05);MMP1基因高表达组HNSCC患者的预后(无病生存期、总生存期)明显差于低表达组(P<0.05)。基因富集分析提示MMP1基因高表达可能在上皮间充质转化、TGF-β信号通路、组织缺氧、血管再生、Noth信号通路、上调KRAS基因信号通路影响肿瘤的生物学进程。结论:MMP1基因高表达与HNSCC患者的发生及发展相关,可作为其独立危险因素,具有较大的临床意义。Abstract: Objective: The aim of this study is to investigate the expression of MMP1 and prognosis in patients with head and neck squamous cell carcinoma (HNSCC), and to identify the potential mechanism of MMP1 in HNSCC.Method: The RNA sequencing data and related clinical data of HNSCC were downloaded from the TCGA public database. The MMP1 gene expression data and corresponding clinical information in the samples were retrospectively analyzed; The data of gene microarray were used to verify the correlation between MMP1 gene and HNSCC. The disease free survival and overall survival of HNSCC were also analyzed; Gene set enrichment analysis was conducted to identify the potential mechanism of MMP1 in HNSCC.Result: Among the 332 HNSCC patients, the expression of MMP1 was significantly associated with lymphatic invasion and tumor grade (P<0.01). The higher the expression level of MMP1 was, the more susceptible the patient was to lymph node metastasis. The data confirmed that the expression of MMP1 in HNSCC was significantly higher than that in normal mucosa (P<0.05); HNSCC of patient in MMP1 high expression group proved to have worse disease free survival and overall survival than in MMP1 low expression group (P<0.05); Gene enrichment analysis indicates that the high expression of MMP1 gene might influence the biological process of tumor though epithelial mesenchymal transition, TGF-β signaling pathway, hypoxia, angiogenesis, Noth signaling pathway, and up-regulation of KRAS gene signaling pathway.Conclusion: The high expression of MMP1 was related with occurrence and development of HNSCC, which can be used as an independent risk factor and has a great clinical significance.
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Key words:
- head and neck neoplasms /
- squamous cell cancer /
- MMP1 /
- gene expression /
- prognosis
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