基质金属蛋白酶及其抑制剂在喉鳞癌中的基因表达谱及临床病理特征相关性分析
Correlation analysis of gene expression profile of matrix metalloproteinases and their inhibitors in laryngeal squamous cell carcinoma and clinicopathological features
倪荣生 1沈晓辉 2高下2
作者信息
- 1. 南通大学附属南京江北医院 耳鼻咽喉头颈外科,江苏 南京 210044
- 2. 南京大学医学院附属鼓楼医院 耳鼻咽喉头颈外科,江苏 南京 210008
- 折叠
摘要
目的 分析喉鳞状上皮细胞癌(laryngeal squamous cell carcinoma,LSCC)中基质金属蛋白酶(matrix metalloproteinase,MMPs)家族及组织金属蛋白酶抑制剂(tissue inhibitors of matrix metalloproteinases,TIMPs)的基因表达谱,找出与LSCC相关性最高的基因进行进一步研究,探讨其蛋白的表达与临床病理特征相关性.方法 选取 28 例LSCC患者,采用含人类全基因组的基因芯片来检测MMPs及TIMPs在 4 例LSCC患者中共同上调或下调的基因.采用逆转录聚合酶链反应(reverse tran-scription-polymerase chain reaction,RT-PCR)及western blot检测24 例患者该基因和蛋白的表达来验证基因芯片结果,并研究该蛋白的表达与临床病理特征之间的关系.结果 基因芯片显示MMPs家族在LSCC与癌旁正常细胞之间的差异表达基因有14 个,其中 4 个基因仅表达上调,4 个基因仅表达下调,另有 6 个基因在部分患者中表达上调,而在另一部分患者中表达下调.未发现在 4 例患者中共同表达上调或下调的基因.TIMPs在LSCC与癌旁正常细胞之间全部表达下调,TIMP4 在 4 例患者中全部表达下调.RT-PCR检测结果显示TIMP4 基因在LSCC组织中低表达.western blot检测结果显示TIMP4 蛋白在LSCC组织中低表达,且TIMP4 蛋白的表达与淋巴结转移相关.结论 研究首次发现MMPs家族及TIMPs在LSCC的表达谱,并发现TIMP4 蛋白的表达与LSCC临床病理特征相关.未来TIMP4 蛋白可能作为LSCC潜在的治疗靶点.
Abstract
Objective The study aimed to discover the gene expression profiles of the matrix metalloproteinases(MMPs)family and tissue inhibitors of matrix metalloproteinases(TIMPs)in laryngeal squamous cell carcinoma(LSCC),to analyze the genes most relevant to LSCC,and finally clarify their relationship with clinicopathological features.Methods Twenty-eight patients with LSCC were studied.In four patients,genes in the MMPs family and TIMPs that are up-regulated or down-regulated simultaneously were detected by a gene chip containing the entire human genome.The gene chip results were verified by reverse transcription-polymerase chain reaction(RT-PCR)and western blot in the other 24 patients.The correlation between the expression of the proteins encoded by the genes and the clinicopathological characteristics of the patients were investigated.Results The gene chip analysis revealed 14 differentially expressed genes of MMPs family between LSCC and adjacent normal cells.Of these,four genes were up-regulated,four were down-regulated,and the remaining six were up-regulated in some patients and down-regulated in others.No genes were consistently up-or down-regulated in the four patients.In contrast,all TIMPs were down-regulated between LSCC and adjacent nor-mal cells.The TIMP4 gene was down-regulated in all four patients.RT-PCR and western blot results showed that the TIMP4 gene and protein was poorly expressed,respectively,in LSCC tissue.Western blot also showed that the expression of TIMP4 protein was correlated with lymph node metastasis.Conclusion To our knowledge,this is the first description of the expression profile of MMPs and TIMPs in LSCC.The expression of TIMP4 protein was associated with the clinicopathological features of LSCC.Future studies may further confirm TIMP4 protein as a predictor of the survival of patients with LSCC and/or a potential therapeutic target of LSCC.
关键词
基因芯片/喉鳞状上皮细胞癌/基质金属蛋白酶/组织金属蛋白酶组织抑制剂Key words
Gene chip/Laryngeal squamous cell carcinoma/Matrix metalloproteinase/Tissue inhibitor of metalloproteinase引用本文复制引用
出版年
2024
NETL
NSTL
万方数据