【作者】 肖仁栋；

【导师】 涂远荣；

【作者基本信息】 福建医科大学 ， 肿瘤学， 2011， 硕士

【摘要】 目的检测食管鳞癌组织中信号转导子和转录激活子3(STAT3)在mRNA、蛋白质和蛋白质磷酸化3种水平的表达,探讨其在食管鳞癌发生、发展、浸润、转移中作用。方法应用Real-Time PCR和Western Blot法分别检测43例食管鳞癌组织中STAT3mRNA、STAT3和磷酸化STAT3(pSTAT3)的表达,并与癌旁正常食管组织进行对照研究,分析STAT3mRNA、STAT3和pSTAT3的表达与临床病理参数的关系。结果⑴食管鳞癌组织中STAT3 mRNA相对表达强度比值(1.43±0.59)较癌旁组织的比值(0.98±0.47)明显增高(P<0.05);食管鳞癌组织中STAT3、pSTAT3表达(2.16±0.39;1.40±0.15)也都显著高于癌旁组织(1.87±0.29;1.25±0.13)(P <0.05);⑵食管鳞癌组织中STAT3mRNA、STAT3和pSTAT3在肿瘤不同分化级别中有表达差异,分化级别越低,表达水平越高(P<0.05),与肿瘤分化级别呈负相关(-1<r<-0.301,P<0.05);它们在TNM分期中Ⅲ期组表达均高于Ⅰ～Ⅱ期组(P<0.05),伴有淋巴结转移组表达也都高于无淋巴结转移组(P<0.05),并与二者呈正相关(二者均为0.301<r<1,P<0.05);但未发现它们在性别、年龄、家族史、吸烟史中有明显表达差异(P>0.05)。结论食管鳞癌组织中STAT3和pSTAT3高表达,尤其活化状态的pSTAT3更为显著,并与食管鳞癌的分化、浸润、转移相关。推断pSTAT3可为食管癌的基因治疗提供理想靶点。目的检测食管鳞癌组织中细胞因子信号转导负调控因子3(SOCS3)的DNA甲基化、mRNA及蛋白表达水平,探讨其在食管鳞癌发生、发展、浸润和转移中的作用。方法应用MSP、Real-Time PCR和Western Blot法分别检测43例食管鳞癌组织中SOCS3的DNA甲基化、mRNA和蛋白表达水平,并与相应的癌旁正常食管组织进行对照研究,分析其与临床病理参数的相关性。结果本组43例实验样本中⑴食管鳞癌组织SOCS3 DNA甲基化的阳性率(79.1%)明显高于癌旁组织(14.0%)(P<0.01);⑵食管鳞癌组织SOCS3mRNA相对表达强度比值(0.53±0.30)明显低于癌旁组织(1.15±0.44)(P<0.01),食管鳞癌组织中甲基化组的SOCS3 mRNA表达(0.45±0.24)显著低于非甲基化组(0.86±0.29) (P<0.05);食管鳞癌组织SOCS3蛋白表达(1.66±0.22)显著低于癌旁组织(1.83±0.15)(P<0.01),食管鳞癌组织中甲基化组SOCS3蛋白表达(1.61±0.21)显著低于非甲基化组(1.87±0.15)(P<0.01);⑶食管鳞癌组织中SOCS3mRNA表达及其蛋白表达水平与肿瘤分化级别呈正相关(0.301<r<1,P<0.05),分化级别越低,表达水平越低(P<0.05),与TNM分期、淋巴结转移呈负相关(-1<r<-0.301,P<0.05),在TNM分期中Ⅲ期组表达均低于Ⅰ～Ⅱ期组(P<0.05);伴有淋巴结转移组表达也都低于无淋巴结转移组(P<0.05);未发现其在性别、年龄、家族史、吸烟史中有明显差异(P>0.05)。结论食管鳞癌组织中SOCS3 DNA甲基化阳性率高,导致SOCS3基因表达下调,与食管鳞癌的分化、浸润和转移密切相关;检测食管鳞癌组织中SOCS3及其DNA甲基化程度可作为判断食管鳞癌恶性程度及生物学行为的重要指标。更多还原

【Abstract】 Objective By testing the expression of signal transducer and activator of transcription 3 (STAT3) in esophageal squamous cell carcinoma (ESCC) tissue at mRNA, protein and protein phosphorylation levels, we studied the function of STAT3 in the occurrence, development, invasion and metastasis of ESCC.Methods By using adjacent normal esophageal tissue as control, the expression of STAT3mRNA, STAT3 and phosphorylated STAT3 (pSTAT3) in 43 cases of ESCC was studied by Real-Time PCR and Western Blot, and subsequently analyzed to find out the correlation with Clinical Pathological Parameters.Results (1) Remarkably higher relative expression intensity of STAT3 at mRNA was found in ESCC tissue( 1.43±0.59) , compared with normal esophageal tissue(0.98±0.47)(P<0.05);STAT3 and pSTAT3 expression in ESCC (2.16±0.39;1.40±0.15)was also significantly higher than normal tissue( 1.87±0.29;1.25±0.13)(P<0.05). (2) Statistical differences were found in different differentiation degrees of tumor for the expression of STAT3mRNA, STAT3 and pSTAT3 in ESCC. The lower differentiation degree, the higher the expression( P< 0.05) . The expression was negatively correlated with differentiation degree of tumor( -1< r<-0.301,P<0.05), while it had a positive relationship with TNM staging and lymph node metastasis( 0.301< r< 1,P< 0.05).In TNM staging, higher expression was found in StageⅢthan both StageⅠand StageⅡ( P< 0.05), and the expression in the group with lymph node metastasis was higher than that in the group without lymph node metastasis( P< 0.05). No obvious connection was found with the age, gender, family history and smoking history of patients( P> 0.05) .Conclusion Higher expression of STAT3 and pSTAT3 in ESCC tissue indicated close correlation with the differentiation, invasion and metastasis of ESCC. pSTAT3 is more significant.Testing of pSTAT3 might provide ideal target for gene therapy of esophageal cancer. Objective By testing the expression of suppressor of cytokine signaling 3 (SOCS3) in esophageal squamous cell carcinoma (ESCC) tissue at DNA methylation, mRNA and protein levels, we studied the function of SOCS3 in the occurrence, development, invasion and metastasis of ESCC.Methods In this study, by using adjacent normal esophageal tissue as control, the expression of SOCS3 DNA methylation, SOCS3 mRNA and SOCS3 protein in 43 cases of ESCC was detected by MSP, Real-Time PCR and Western Blot, and subsequently analyzed to find out the correlation with Clinical Pathological Parameters.Results (1) The positive rate of SOCS3 DNA methylation in ESCC( 79.1%) was significantly higher than normal tissue( 14.0%)( P< 0.01). (2) Remarkably lower relative expression intensity of SOCS3 mRNA was found in ESCC tissue (0.53±0.30), compared with normal esophageal tissue(1.15±0.44)( P﹤0.01) . In ESCC, the SOCS3mRNA expression was notably lower in methylation group(0.45±0.24) than non-methylation group(0.86±0.29)( P<0.05). (3) SOCS3 protein expression in ESCC(1.66±0.22) was also evidently lower than adjacent normal tissue (1.83±0.15)( P <0.01). In ESCC, the SOCS3 expression was notably lower in methylation group(1.61±0.21) than non-methylation group(1.87±0.15)( P <0.01). (4) Expression of both SOCS3mRNA and SOCS3 in ESCC was positively correlated with differentiation degree ( P < 0.05 ) , while it had a negative correlation with TNM staging and lymph node metastasis( P< 0.05) . No obvious connection was found with the age, gender, family history and smoking history of patients( P> 0.05) .Conclusion The decrease of SOCS3 gene expression in ESCC was caused by the high positive rate of SOCS3 DNA methylation, which was closely connected with the differentiation, invasion and metastasis of ESCC. The detection of SOCS3 DNA methylation,SOCS3mRNA and SOCS3 expression in ESCC could provide important index in diagnosis of the malignant degree and biological behavior of esophageal squamous cell carcinoma.更多还原