摘要
目的本研究通过分析喉鳞状细胞癌(简称喉癌)及其癌旁组织中转移相关蛋白2(metastasis associated protein 2,MTA2)、锌指转录蛋白(zinc finger transcription protein,Slug)和基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)的表达及与临床病理参数和患者预后的关系,探讨其在喉癌发生发展中的作用及临床意义。方法采用免疫组织化学SP法检测MTA2,Slug和MMP-9在喉癌及癌旁组织中的表达,χ2检验分析三种蛋白与临床病理因素的关系,Spearman相关分析评估MTA2与Slug及MMP-9的相关性;采用Western Blot法检测MTA2、Slug与MMP-9蛋白的相对表达量;生存曲线绘制采用Kaplan-Meier法、组间差异及三种蛋白的高表达对5年生存期的影响利用Log-rank检验证实。结果免疫组化结果表明MTA2、Slug与MMP-9蛋白在喉癌组织中的阳性表达率均高于癌旁组织,分别为10.00%和73.33%,16.67%和75.56%,20.00%和71.11%。MTA2和Slug的蛋白表达与喉癌主要临床病理参数显著相关,包括淋巴结转移、临床分期和肿瘤分化程度(P均<0.05);高表达的MMP-9与喉癌高临床分期和淋巴结转移成正相关(P均<0.05)。对45例喉癌组织进行相关性分析发现,MTA2和Slug蛋白表达(r=0.592,P=0.000)及MMP-9蛋白表达(r=0.392,P=0.008)均呈正相关。Western blot结果也证实MTA2、Slug与MMP-9蛋白在喉癌组织中表达高于癌旁组织。生存分析发现,MTA2、Slug与MMP-9蛋白阳性表达均提示患者较短的5年生存期(P均<0.05)。结论高表达的MTA2、Slug与MMP-9提示喉癌进展和患者的不良预后,MTA2结合Slug与MMP-9可能成为喉癌进展及患者预后评估的潜在标志物,针对三种标志物有可能会为喉癌患者制定新的治疗策略。
OBJECTIVE To investigate the expression of metastasis associated protein 2(MTA2),zinc finger transcription protein(Slug)and matrix metalloproteinase 9(MMP-9)protein in laryngeal squamous cell carcinoma(LSCC)tissues and adjacent tissues,as well as to determine possible relationships of three proteins with both the clinicopathological parameters and the prognosis of the patients,and to discuss the roles and clinical significance of the three proteins in the process of laryngeal squamous cell carcinogenesis.METHODS Immunohistochemistry was used to detect the expressions of MTA2,Slug and MMP-9 in LSCC samples and corresponding adjacent samples,Chi-square test was used to assess three markers with clinicopathological parameters,Spearman’s correlation test was used to assess the relationship of MTA2 and other two markers.Western Blot was used to examine the relative expression of MTA2,Slug and MMP-9.Survival curves were obtained by the Kaplan-Meier method,The log rank test was used to compare differences in survival rates between two groups and confirm the high expression of three markers on influencing 5-year overall survival rate.RESULTS We observed increased expression of MTA2(10.00% and 73.33%),Slug(16.67% and 75.56%)and MMP-9(20.00% and 71.11%)in LSCC when compared with adjacent tissues,MTA2 and Slug expressions were significantly associated with the majority of clinicopathological parameters assessed,including lymph node metastases,clinical stage and tumor cell differentiation(all P<0.05).Higher level of MMP-9 expression positively correlated with a more advanced tumor stage and lymph node metastasis(both P<0.05).The Spearman’s correlation test revealed that the MTA2 expression was significantly positively associated with both Slug(r=0.592,P=0.000)and MMP-9(r=0.392 P=0.008)expression in the 45 laryngeal squamous cell carcinoma specimens.Our Western blot data also confirmed that the expressions of MTA2,Slug and MMP-9 were significantly up-regulated in LSCC compared to the adjacent non-neoplastic laryngeal tissue.As calculated through Kaplan-Meier method,patients with MTA2,Slug and MMP-9 positive expression showed lower overall survival rates(all P<0.05).CONCLUSION Overexpression of MTA2,Slug and MMP-9 in human LSCC might be used to predict tumor progression and poor prognosis.MTA2 combined with Slug and MMP-9 are potential markers for tumor progression and prognosis assessment,and targeting them may be a novel valuable strategy for the treatment of LSCC.
作者
刘玉东
甄娟
韩晓丽
郭明丽
LIU Yudong;ZHEN Juan;HA N Xiaoli;GUO Mingli(Department of Otolaryngology,Hebei General Hospital,Shijiazhuang,Hebei,050011,China;Department of Pathology,the Fourth Hospital of Shijiazhuang,Shijiazhuang,Hebei,050011,China)
出处
《中国耳鼻咽喉头颈外科》
CSCD
2020年第9期507-511,共5页
Chinese Archives of Otolaryngology-Head and Neck Surgery
基金
河北省医学科学研究重点课题计划(20190346)。
关键词
癌
鳞状细胞
基质金属蛋白酶9
免疫组织化学
预后
转移相关蛋白2
锌指转录蛋白
Carcinoma,Squamous Cell
Matrix Metalloproteinase 9
Immunohistochemistry
Prognosis
metastasis associated protein 2
zinc finger transcription protein
