DNMT1和PDCD4在舌鳞状细胞癌中的表达及临床意义

发布时间：2018-12-14 07:47

【摘要】：目的研究DNA甲基转移酶1（DNMT1）蛋白与程序性细胞死亡因子4（PDCD4）蛋白在舌鳞状细胞癌(TSCC)组织及癌旁非肿瘤组织中的表达情况，同时分析二者蛋白表达水平的关系，与舌鳞状细胞癌患者的年龄、性别、组织病理分型、TNM分期、有无淋巴结转移等临床病理学参数之间的关系，并探讨两因子在舌鳞癌发生发展中的作用，两种蛋白的表达能否作为舌鳞癌早期诊断、治疗及临床预后评价的依据。方法采用免疫组化Elivision二步法检测40例舌鳞状细胞癌组织及相对应的癌旁非肿瘤组织中DNMT1与PDCD4蛋白的表达情况；应用SPSS17.0统计软件对结果进行统计学分析，研究两因子蛋白表达水平及其与患者年龄、性别、组织病理分型、临床分期、有无淋巴结转移等临床病理学参数之间的关系。结果 1.在40例舌鳞状细胞癌组织中有29例DNMT1蛋白表达呈阳性（阳性率72.5%）。40例相对应的癌旁非肿瘤组织中仅有5例呈阳性表达（阳性率12.5%）。DNMT1在舌鳞状细胞癌与癌旁非肿瘤组织中的蛋白表达有显著差异（P0.05）。 2.在40例舌鳞状细胞癌组织中有12例PDCD4蛋白表达呈阳性（阳性率30.0%）。40例相对应的癌旁非肿瘤组织中31例呈阳性表达（阳性率77.5%）。PDCD4在舌鳞状细胞癌与癌旁非肿瘤组织中的蛋白表达有显著差异（P0.05）。 3.舌鳞状细胞癌组织中DNMT1蛋白表达水平与组织病理分型、有无淋巴结转移及TNM分期有关（P0.05)，与患者的性别、年龄无关（P0.05)。 4.舌鳞状细胞癌组织中PDCD4蛋白表达水平与有无淋巴结转移及TNM分期有关（P0.05)，与患者的性别、年龄、组织病理分型无关（P0.05)。 5.40例舌鳞癌患者有5例两蛋白表达均为阳性，4例均为阴性，采用Spearman秩相关分析得出两蛋白在舌鳞癌中的表达呈负相关（r=－0.452，P0.05)。结论 1.在舌鳞癌组织中DNMT1蛋白呈高表达，PDCD4呈低表达；而相对应的癌旁非肿瘤组织中两者的表达情况则相反。提示两种蛋白表达水平的变化与舌鳞癌的发生发展有密切关系。 2. DNMT1蛋白表达水平与组织病理分型、有无淋巴结转移及TNM分期有关（P0.05)，与患者的性别、年龄无关（P0.05)；而PDCD4的表达则只与淋巴结转移及TNM分期相关（P0.05)，，与其性别、年龄及组织病理分型无关（P0.05)。 3. DNMT1是表观遗传学中DNA进行甲基化的关键酶，PDCD4是抑癌基因，两者在舌鳞癌中的表达呈负相关（r=－0.452，P0.05)。DNA甲基化是肿瘤发生发展的早发事件，过甲基化能沉默PDCD4基因的表达。在此研究中，我们推测某种原因或者通过某种通路使甲基化的相关酶DNMT1表达增高，此酶增高可促使PDCD4过甲基化，而使PDCD4基因沉默蛋白表达从而减少。正常舌组织中癌基因和抑癌基因表达处于平衡状态，当抑癌蛋白减少会引起舌鳞癌的发生。由此得出DNMT1可能通过氋甲基化的方式负向调节PDCD4基因的表达致肿瘤发生。
[Abstract]:Objective to study the expression of DNA methyltransferase 1 (DNMT1) protein and programmed cell death factor 4 (PDCD4) protein in squamous cell carcinoma of tongue (TSCC) and adjacent non-tumor tissues. At the same time, the relationship between the expression level of protein and age, sex, histopathology, TNM staging, lymph node metastasis and other clinicopathological parameters in patients with tongue squamous cell carcinoma was analyzed. To explore the role of two factors in the occurrence and development of tongue squamous cell carcinoma, and whether the expression of two proteins can be used as the basis for early diagnosis, treatment and clinical prognosis evaluation of tongue squamous cell carcinoma. Methods the expression of DNMT1 and PDCD4 protein in 40 cases of tongue squamous cell carcinoma and its adjacent non-tumor tissues were detected by immunohistochemical Elivision two-step method. To study the relationship between the expression of two factor protein and the clinical pathological parameters such as age, sex, histopathologic type, clinical stage, lymph node metastasis and so on. Result 1. Of the 40 cases of tongue squamous cell carcinoma, 29 cases (72.5%) were positive for DNMT1 protein, and only 5 cases (12.5%) were positive for DNMT1 in adjacent non-tumor tissues. There was significant difference in the expression of protein between cancer and non-tumor tissues (P 0.05). 2. Of the 40 cases of tongue squamous cell carcinoma, 12 cases (30.0%) were positive for PDCD4 protein, and 31 cases (77.5%) were positive for PDCD4 in non-cancerous adjacent tissues. There was significant difference in the expression of protein between cancer and adjacent non-tumor tissues (P 0.05). 3. The expression of DNMT1 protein in tongue squamous cell carcinoma was related to histological type, lymph node metastasis and TNM stage (P0.05), but not to sex and age (P0.05). 4. The expression of PDCD4 protein in tongue squamous cell carcinoma was correlated with lymph node metastasis and TNM stage (P0.05), but not with sex, age and histological type (P0.05). 5.The expression of two proteins in 5 cases of tongue squamous cell carcinoma was positive in 5 cases and negative in 4 cases. The expression of two proteins in tongue squamous cell carcinoma was negatively correlated by Spearman rank correlation analysis (r-0.452p0.05). Conclusion 1. In tongue squamous cell carcinoma, the expression of DNMT1 protein was high and PDCD4 was low, but the expression of both proteins was opposite in the adjacent non-tumor tissues. These results suggest that the changes of the expression level of the two proteins are closely related to the development of tongue squamous cell carcinoma. 2. The expression of DNMT1 protein was related to histopathologic type, lymph node metastasis and TNM stage (P0.05), but not to sex and age (P0.05). The expression of PDCD4 was only correlated with lymph node metastasis and TNM stage (P0.05), but not with sex, age and histopathologic type (P0.05). 3. DNMT1 is the key enzyme of DNA methylation in epigenetics, and PDCD4 is a tumor suppressor gene. The expression of PDCD4 and PDCD4 in tongue squamous cell carcinoma is negatively correlated (r = -0.452P 0.05). DNA methylation is an early event in tumorigenesis and progression. Hypermethylation can silence the expression of PDCD4 gene. In this study, we speculated that the expression of methylation-related enzyme DNMT1 was increased for some reason or through some pathway, which could promote hypermethylation of PDCD4 and decrease the expression of silencing protein of PDCD4 gene. The expression of oncogene and tumor suppressor gene is in balance in normal tongue tissue. When the tumor suppressor protein is reduced, it will cause the development of tongue squamous cell carcinoma. It is concluded that DNMT1 may negatively regulate the expression of PDCD4 gene by methylation.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.86

【参考文献】