Expression levels of MMP-14, ING4 and HIF-1α in 60 patients with oral squamous cell carcinoma and their clinical significance

doi:10.19439/j.sjos.2020.06.016

Abstract

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

CLC Number:

R739.8

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.

References

[1] 杨永超, 段峰, 张璇. TGF-β1、PTEN在口腔鳞癌组织中的表达及意义[J]. 黑龙江医药科学, 2017, 40(3): 72-74.
[2] 陈新, 徐文华, 周健, 等. 口腔鳞状细胞癌现状[J].口腔医学, 2017, 37(5): 462-465.
[3] 赵全刚. 研究口腔颌面部鳞癌手术治疗的临床效果[J].中国社区医师, 2017, 33(7): 75-75.
[4] 赵晓苇, 周静萍, 毕于蓝, 等. PI3K/AKT信号通路在促进口腔鳞癌侵袭转移中的作用[J]. 皖南医学院学报, 2019, 38(1): 75-79.
[5] 郭玉霞, 郑绘霞. ING4在卵巢肿瘤中的表达及意义[J].山西医科大学学报, 2018, 49(10): 1211-1213.
[6] 黄星星. ING4抑制结直肠癌EMT和转移的作用及其机制研究[D]. 苏州: 苏州大学, 2018.
[7] 孙立园, 赵杨, 刘莎莎, 等. 结直肠癌中IGF-1、IGFBP-3、MMP-14的表达及意义[J]. 临床与实验病理学杂志, 2018, 34(10): 1072-1075.
[8] 李欢, 王世全, 焦健. 乳腺浸润性导管癌中NM23、基质金属蛋白酶-2和-14的表达及意义[J]. 中国老年学杂志, 2016, 36(17): 4232-4234.
[9] 廖文胜, 李江发, 何阳阳. 原发性肝细胞癌组织中磷脂酶CE1和基质金属蛋白酶-14的表达及意义[J].中国老年学杂志, 2018, 38(11): 2609-2610.
[10] 刘月平, 刘俊英, 郭瑞霞, 等. 肺腺癌中MMP-9、MMP-13、HIF-1α表达与临床病理特征、EGFR突变及预后的关系[J].临床与实验病理学杂志, 2017, 33(11): 1188-1193.
[11] 张展, 李鹏云, 闫欢, 等. 缺氧微环境中HIF-1α基因沉默的人绒毛膜癌细胞系JE G-3侵袭和迁移能力观察[J]. 山东医药, 2018, 58(3): 15-18.
[12] 施宣忍, 刘群, 王莉, 等.缺氧微环境下HIF-1α对卵巢癌A2780细胞侵袭转移的影响及分子机制[J]. 现代妇产科进展, 2017, 26(3): 174-178.
[13] Zhao D, Liu X, Zhang Y, et al.Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma[J]. Oncol Lett, 2016, 11(4): 2869-2874.
[14] 张龙军, 刘健, 曹凤宏, 等. 结蛋白在前列腺增生和前列腺癌中的差异性表达及临床意义[J]. 四川医学, 2016, 38(8): 894-898.
[15] 毕也, 周童, 贾颜鸿, 等. MMP-14在口腔癌患者预后及转移的临床病理学研究[J]. 口腔医学, 2018, 38(8): 685-689.
[16] 代魏魏, 唐丽萍, 卢文. ING4基因的抗肿瘤作用研究进展[J]. 现代肿瘤医学, 2016, 24(17): 2827-2830.
[17] 彭芳, 钟斌, 王建, 等. ING4在结肠和直肠的胃肠间质瘤表达的研究[J]. 实验与检验医学, 2017, 35(3): 337-339,343.
[18] 孟颖. ING4通过逆转上皮-间充质转化(EMT)抑制乳腺癌细胞的迁移和侵袭[D]. 苏州: 苏州大学, 2016.
[19] 夏中友, 伍季, 张萌, 等. 前列腺癌组织中ING4与VEGF的表达及相关性研究[J]. 西部医学, 2017, 29(2): 187-191,195.
[20] Conlon G, Murray G.Recent advances in understanding the roles of matrix metalloproteinases in tumour invasion and metastasis[J]. J Pathol, 2019, 247(5):629-640.
[21] 张洋洋, 任东红, 公建庄. 基质金属蛋白酶14的表达对食管癌细胞迁移、侵袭能力的影响及其作用机制的研究[J].临床内科杂志, 2018, 35(3): 189-191.
[22] 陈晓燕. MMP-14和Ezrin在子宫内膜癌中的表达和临床意义分析[J].检验医学与临床, 2017,14(9): 1344-1346.
[23] 王禹锟, 郭婧玉, 孙越, 等.成釉细胞瘤中基质金属蛋白酶12、14和细胞角蛋白7的表达及相关性[J].中国老年学杂志, 2018,38(12): 2876-2878.
[24] Liu J, Zhang C, Zhao Y, et al.Parkin targets HIF-1α for ubiquitination and degradation to inhibit breast tumor progression[J]. Nat Commun, 2017, 8(1): 1823-1823.
[25] 甄娟, 刘玉东, 宋春红, 等. 卵巢癌组织中泛素连接酶SIAH2、HIF-1α蛋白的表达观察[J].山东医药, 2018, 58(35): 64-66.