【摘要】：目的 研究DNA甲基轉移酶1（DNMT1）蛋白與程序性細胞死亡因子4（PDCD4）蛋白在舌鱗狀細胞癌(TSCC)組織及癌旁非腫瘤組織中的表達情況，同時分析二者蛋白表達水平的關系，與舌鱗狀細胞癌患者的年齡、性別、組織病理分型、TNM分期、有無淋巴結轉移等臨床病理學參數(shù)之間的關系，并探討兩因子在舌鱗癌發(fā)生發(fā)展中的作用，兩種蛋白的表達能否作為舌鱗癌早期診斷、治療及臨床預后評價的依據(jù)。 方法 采用免疫組化Elivision二步法檢測40例舌鱗狀細胞癌組織及相對應的癌旁非腫瘤組織中DNMT1與PDCD4蛋白的表達情況；應用SPSS17.0統(tǒng)計軟件對結果進行統(tǒng)計學分析，研究兩因子蛋白表達水平及其與患者年齡、性別、組織病理分型、臨床分期、有無淋巴結轉移等臨床病理學參數(shù)之間的關系。 結果 1.在40例舌鱗狀細胞癌組織中有29例DNMT1蛋白表達呈陽性（陽性率72.5%）。40例相對應的癌旁非腫瘤組織中僅有5例呈陽性表達（陽性率12.5%）。DNMT1在舌鱗狀細胞癌與癌旁非腫瘤組織中的蛋白表達有顯著差異（P0.05）。 2.在40例舌鱗狀細胞癌組織中有12例PDCD4蛋白表達呈陽性（陽性率30.0%）。40例相對應的癌旁非腫瘤組織中31例呈陽性表達（陽性率77.5%）。PDCD4在舌鱗狀細胞癌與癌旁非腫瘤組織中的蛋白表達有顯著差異（P0.05）。 3.舌鱗狀細胞癌組織中DNMT1蛋白表達水平與組織病理分型、有無淋巴結轉移及TNM分期有關（P0.05)，與患者的性別、年齡無關（P0.05)。 4.舌鱗狀細胞癌組織中PDCD4蛋白表達水平與有無淋巴結轉移及TNM分期有關（P0.05)，與患者的性別、年齡、組織病理分型無關（P0.05)。 5.40例舌鱗癌患者有5例兩蛋白表達均為陽性，4例均為陰性，采用Spearman秩相關分析得出兩蛋白在舌鱗癌中的表達呈負相關（r=－0.452，P0.05)。 結論 1.在舌鱗癌組織中DNMT1蛋白呈高表達，PDCD4呈低表達；而相對應的癌旁非腫瘤組織中兩者的表達情況則相反。提示兩種蛋白表達水平的變化與舌鱗癌的發(fā)生發(fā)展有密切關系。 2. DNMT1蛋白表達水平與組織病理分型、有無淋巴結轉移及TNM分期有關（P0.05)，與患者的性別、年齡無關（P0.05)；而PDCD4的表達則只與淋巴結轉移及TNM分期相關（P0.05)，，與其性別、年齡及組織病理分型無關（P0.05)。 3. DNMT1是表觀遺傳學中DNA進行甲基化的關鍵酶，PDCD4是抑癌基因，兩者在舌鱗癌中的表達呈負相關（r=－0.452，P0.05)。DNA甲基化是腫瘤發(fā)生發(fā)展的早發(fā)事件，過甲基化能沉默PDCD4基因的表達。在此研究中，我們推測某種原因或者通過某種通路使甲基化的相關酶DNMT1表達增高，此酶增高可促使PDCD4過甲基化，而使PDCD4基因沉默蛋白表達從而減少。正常舌組織中癌基因和抑癌基因表達處于平衡狀態(tài)，當抑癌蛋白減少會引起舌鱗癌的發(fā)生。由此得出DNMT1可能通過氋甲基化的方式負向調(diào)節(jié)PDCD4基因的表達致腫瘤發(fā)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.
【學位授予單位】：南昌大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R739.86

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