MMP-14、ING4和HIF-1α在60例口腔鳞癌中的表达及临床意义

doi:10.19439/j.sjos.2020.06.016

摘要/Abstract

摘要： 目的： 探讨人口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC）组织中金属基质蛋白酶14（metallomatrix protease-14, MMP-14）、生长抑制因子4（inhibitor of growth family 4, ING4）和缺氧诱导因子1α（hypoxia-inducible?factor-1α, HIF-1α）的表达及临床意义,为OSCC的临床诊疗提供依据。方法： 选择东南大学附属中大医院2014年7月—2019年7月收治的60例口腔鳞癌确诊患者为研究对象,将口腔鳞癌组织制备成石蜡切片,作为实验组;另取20例正常口腔黏膜（NOM）组织石蜡切片作为对照组。应用免疫组织化学S-P法分析2组口腔黏膜组织中MMP-14、ING4和HIF-1α的阳性表达,并分析其与OSCC临床病理特征之间的关系以及3种蛋白表达的相关性。采用SPSS 23.0软件包对数据进行统计学分析。结果： OSCC患者组织中的ING4阳性表达率为41.7%（25/60）,显著低于对照组的70.0%（14/20）（P<0.05）;MMP-14和HIF-1α的阳性表达率分别为68.3%（41/60）、71.7%（43/60）,显著高于对照组的20.0%（4/20）、15.0%（3/20）（P<0.01）。3种蛋白的阳性表达率与OSCC的TNM分期、分化程度以及是否有颈淋巴结转移显著有关（P<0.05）。在OSCC组织中,ING4与HIF-1α或MMP-14的表达呈显著负相关关系（r=-0.39, -0.51, P<0.01）,而HIF-1α和MMP-14的表达则呈显著正相关关系（r=0.45, P<0.01）。结论： MMP-14、ING4和HIF-1α与口腔鳞癌的进展密切相关,ING4下调能促进MMP-14和HIF-1α上调,最终促进OSCC的形成、生长、侵袭和转移。3种蛋白的表达可作为判断OSCC患者临床特征和预后的重要参考指标。

关键词: 金属基质蛋白酶14, 生长抑制因子4, 缺氧诱导因子1α, 口腔鳞癌, 临床特征

Abstract: PURPOSE: To investigate the expression of metalloproteinase-14 (MMP-14), growth inhibitory factor 4 (ING4) and hypoxia-inducible factor-1α (HIF-1α) in human oral squamous cell carcinoma (OSCC) and their clinical significance, to provide references for clinical diagnosis and treatment of OSCC. METHODS: Sixty patients with OSCC admitted to our hospital from July 2014 to July 2019 were enrolled in this study. The tissue specimen of 60 patients were prepared into paraffin sections as the experimental group, while 20 cases of normal oral mucosal tissue were paraffin-embedded as the control group. Immunohistochemical S-P method was used to analyze the positive expression levels of MMP-14, ING4 and HIF-1α in oral mucosa of the two groups. The relationship between the 3 indicators and the different clinicopathological features of OSCC patients was analyzed, the correlation of the expression level between 3 protein was also calculated. SPSS 23.0 software package was used for statistical analysis of the data. RESULTS: The positive expression rate of ING4 in OSCC patients was 41.7% (25/60), which was significantly lower than 70.0% (14/20) in the control group (P<0.05). The positive expression rates of MMP-14 and HIF-1α were 68.3% (41/60), 71.7% (43/60), respectively, significantly higher than 20.0% (4/20) and 15.0% (3/20) of the control group. The difference between the 2 groups was statistically significant (P<0.01). The positive expression rate of the 3 proteins was significantly correlated with TNM stage, differentiation and cervical lymph node metastasis (P<0.05). In OSCC tissues, there was a significant negative correlation between ING4 and HIF-1α or MMP-14 expression (r=-0.39, -0.51, P<0.01), while HIF-1α and MMP-14 expression was significantly positively correlated with the clinical features (r= 0.45, P<0.01). CONCLUSIONS: MMP-14, ING4 and HIF-1α are closely related to the progression of OSCC. Down-regulation of ING4 can promote up-regulation of MMP-14 and HIF-1α, and ultimately promote formation, growth, invasion and metastasis of OSCC. The expression levels of the 3 proteins can be used as important indicators for judging the clinical features and prognosis of patients with OSCC.

Key words: Metalloproteinase-14, Growth inhibitory factor 4, Hypoxia-inducible factor-1α, Oral squamous cell carcinoma, Clinical features

中图分类号:

R739.8

傅宗云, 陶峰. MMP-14、ING4和HIF-1α在60例口腔鳞癌中的表达及临床意义[J]. 上海口腔医学, 2020, 29(6): 642-646.

FU Zong-yun, TAO Feng. Expression levels of MMP-14, ING4 and HIF-1α in 60 patients with oral squamous cell carcinoma and their clinical significance[J]. Shanghai Journal of Stomatology, 2020, 29(6): 642-646.

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