T-cadherin启动子甲基化与胃癌恶性生物学行为及预后关系的研究

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目的:探讨T-cadherin基因表达及启动子甲基化与胃癌恶性生物学行为及预后的相关性。方法:采用免疫组织化学法(IHC)和甲基化特异性PCR法(MSP)检测80例临床手术切除的胃癌标本及40例相应癌旁组织标本中T-cadherin表达及启动子甲基化情况,并与临床病理资料进行对照分析,每例患者随访24个月。结果:80例胃癌标本中,T-cadherin阳性表达率仅为45.0%(36/80),与相应癌旁组织相比明显减低。T-cadherin表达与组织分型(P=0.032)、肿瘤分化程度(P=0.037)、是否存在淋巴结转移(P=0.010)及TNM分期有关(P=0.000),与患者年龄、性别及肿瘤大小无关(P>0.05)。80例胃癌标本中有38例存在T-cadherin启动子甲基化现象(47.5%),癌旁组织标本则全部呈非甲基化状态(100.0%)。T-cadherin启动子甲基化与组织分型(P=0.012)、肿瘤分化程度(P=0.020)、是否存在淋巴结转移(P=0.020)及TNM分期有关(P=0.007),与患者年龄、性别及肿瘤大小无关(P>0.050)。24个月的随访结果显示:T-cadherin启动子甲基化组的平均生存时间和中位生存时间均较非甲基化组缩短,两组差异有统计学意义(P=0.029)。通过Cox比例风险模型评估,胃癌的分化程度(P=0.030)、是否存在淋巴结转移(P=0.010)及TNM分期(P=0.010)均可影响患者的生存时间,分化程度低、发生淋巴结转移、TNM分期Ⅲ-Ⅳ期的胃癌患者死亡风险增加。结论:T-cadherin启动子甲基化是导致该蛋白表达下调的原因之一,与胃癌恶性生物学行为及预后密切相关,可作为胃癌恶性程度判断及预后评估的参考指标,对指导临床诊治有重要意义。 Objective: To investigate the relationship between T-cadherin gene expression, promoter methylation and malignant behavior and prognosis of gastric cancer. Methods: The expressions of T-cadherin and promoter methylation in 80 surgically resected gastric cancer specimens and 40 corresponding paracancerous tissues were detected by immunohistochemistry (IHC) and methylation-specific PCR (MSP) , And compared with clinicopathological data, each patient was followed up for 24 months. Results: The positive expression rate of T-cadherin in 80 gastric cancer specimens was only 45.0% (36/80), which was significantly lower than that in the corresponding paracancerous tissues. T-cadherin expression correlated with histological type (P = 0.032), tumor differentiation (P = 0.037), presence of lymph node metastasis (P = 0.010) and TNM stage (P = 0.000), but not with age, sex and tumor size Not related (P> 0.05). T-cadherin promoter methylation (47.5%) was found in 38 of 80 gastric cancer samples, and non-methylated (100.0%) in adjacent non-cancerous tissues. The methylation of T-cadherin promoter correlated with histological type (P = 0.012), tumor differentiation (P = 0.020), lymph node metastasis (P = 0.020) and TNM staging Sex and tumor size were not related (P> 0.050). The 24-month follow-up results showed that the mean survival time and median survival time of T-cadherin promoter methylation group were shorter than that of non-methylation group, the difference was statistically significant (P = 0.029). The degree of differentiation (P = 0.030), presence of lymph node metastasis (P = 0.010), and TNM stage (P = 0.010) in gastric cancer patients affected the survival time, the degree of differentiation, the incidence of lymph node metastasis, Patients with TNM stage III-IV gastric cancer have an increased risk of dying. CONCLUSION: Methylation of T-cadherin promoter is one of the reasons for the down-regulation of T-cadherin promoter. It is closely related to the malignant biological behavior and prognosis of gastric cancer. It can be used as a reference index for the judgment of malignant degree and prognosis of gastric cancer. Significance.
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