Ni Haifeng, Jiang Bo, Zhou Zhen, Yuan Xiaoyang, Cao Xiaolin, Huang Guangwu, Li Yong
Department of Otolaryngology, Affiliated Hangzhou First People's Hospital of Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China.
Int J Mol Med. 2017 Sep;40(3):673-678. doi: 10.3892/ijmm.2017.3044. Epub 2017 Jun 27.
The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation‑specific PCR, semi‑quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3‑methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC.
本研究旨在探讨鼻咽癌(NPC)中MutS同源蛋白人类3(MSH3)基因启动子甲基化导致的失活情况。采用甲基化特异性PCR、半定量逆转录PCR和免疫组织化学分析检测54例NPC组织和16例正常鼻咽上皮(NNE)组织中MSH3的甲基化情况以及mRNA和蛋白表达水平。分析启动子甲基化与mRNA表达之间的关联,以及该基因的mRNA和蛋白表达与临床因素之间的关系。在50%(27/54)的原发性肿瘤中检测到MSH3启动子甲基化,而在16例NNE组织中未检测到。与16例NNE组织相比,54例人类NPC组织中的mRNA和蛋白表达水平显著降低(P<0.05)。MSH3甲基化的病例其mRNA和蛋白表达水平显著低于未甲基化的病例(P<0.05)。MSH3的mRNA和蛋白表达水平与T分期显著相关(P<0.05);然而,它们与患者的年龄、性别、N分期、TNM分类或组织病理学亚型无关(P>0.05)。总体而言,MSH3常因启动子甲基化而失活,其mRNA和蛋白表达与NPC的原发性肿瘤分期相关。