【作者】 陈丽；

【导师】 张丽生；

【作者基本信息】 广西医科大学 ， 肿瘤生物治疗， 2003， 硕士

【摘要】 目的：研究TGF-β/SMAD信号通路主要组成分子TGF-β1、TGF-βRⅡ、Smad4、Smad7在原发性肝细胞癌患者肝组织中的表达状况,旨在探讨该信号通路在原发性肝细胞癌发生发展的作用和临床意义。方法：应用半定量逆转录多聚酶链反应（RT-PCR）方法检测39对人肝细胞癌组织、相应癌旁肝组织中TGF-β1、TGF-βRⅡ、Smad4、Smad7的mRNA表达率及表达水平，综合分析它们的表达变化与相应临床指标，包括患者年龄、肿瘤大小、有无胞膜、分化程度、有无门静脉癌栓及患者血清AFP水平的关系。结果：⑴ 39例肝癌组织中TGF-β1mRNA的阳性表达率明显高于癌旁组织（分别为92.3％和71.8％，P<0.05）；TGF-βRⅡmRNA的阳性表达率在癌组织和癌旁组织中无显著差异（分别为43.6％和41.0％，P>0.05）,<WP=5>但两者的缺失率都大于50％；癌组织Smad4mRNA的阳性表达率明显高于癌旁组织（分别为94.9％和74.4％，P<0.05）；而Smad7mRNA的阳性表达率癌组织低于癌旁组织（分别为76.9％和94.4％，P<0.05）。⑵ TGF-β1mRNA和Smad7mRNA均阳性表达的肝癌组织及其癌旁组织中，其表达水平无显著性差异（P分别为0.327和0.491）； 而Smad4 mRNA的表达水平癌组织显著高于癌旁组织（P=0.000）。⑶ TGF-βRⅡ在有胞膜的肿瘤和伴门静脉癌栓的患者中表达阳性率明显高于无胞膜的肿瘤和不伴门静脉癌栓的患者（P＝0.019和P＝0.039）。Smad4、Smad7的阳性表达与患者有无门静脉癌栓有关：Smad4在有门静脉癌栓的患者阳性表达率（10/13）明显低于无门静脉癌栓的患者（26/26）（P＝0.031）；而Smad7在有门静脉癌栓的患者中的阳性表达率（12/13）明显高于无门静脉癌栓的患者（15/26）（P＝0.034）。而TGF-β1、TGF-βRⅡ、Smad4、Smad7mRNA的表达率与患者年龄、肿瘤大小、肿瘤分化程度、AFP值高低及HBsAg感染等临床病理指标无显著性相关。结论：肝细胞癌组织中TGF-β1、TGF-βRⅡ、Smad4、Smad7的表达率及表达水平与相应癌旁组织间显示差异，并且它们的表达与反映肝癌预后的重要临床指标相关，提示TGF-β/SMAD信号通路在肝细胞癌发生发展中可能起重要作用，监测病人该通路中的上述组成分子变化可能有助于临床治疗预后的判断。更多还原

【Abstract】 Objective To explore the roles of TGF-β/SMAD signaling pathway in primary hepatocellular carcinoma(PHC) and its clinical significance， this thesis investigate the expression of TGFβ1,TβRⅡ,Smad4 and Smad7 mRNA，the main component of such signaling pathway，in liver tissue of patients with PHC. Methods TGFβ1,TβRⅡ,Smad4 ，Smad7 expression and its levels were assessed in matched tumorous and corresponding nontumorous liver tissue with semi-quantitative reverse transcription polymerase chain reation (RT-PCR) procedure. Meanwhile，the relationship between these genes mRNA expression and clinical-pathological parameters，such as age, size and differentiation of the tumor, with or without portal vein cancer-embolus, with<WP=7>or without tumor diaphragm and serum AFP level et al. Results ⑴ The positive expression rate of TGFβ1 mRNA in 39 hepatocellular carcinoma tissue were significantly higher than para-cancer liver tissue (92.3% and 71.8% respectively,P<0.05). There are no difference expression rate of TβRⅡmRNA (43.6％ and 41.0％，P>0.05)between hepatocellular carcinoma tissue and para-cancer liver tissue. However, The loss of TβRⅡ both in hepatocellular carcinoma tissue and para-cancer liver tissue were higher than 50% . The positive expression rate of Smad4 mRNA in 39 hepatocellular carcinoma tissue were significantly higher than para-cancer liver tissue (94.9％ and 74.4％ respectively，P<0.05). The positive expression rate of Smad7 mRNA in 39 hepatocellular carcinoma tissue were significantly lower than para-cancer liver tissue (76.9％ and 94.9％ respectively,P<0.05).⑵There are no difference expression level of TGFβ1 mRNA and Smad7 mRNA among cases with both positive results in carcer and para-cancer tissue （P=0.327 and 0.491）.The expression level of Smad4 mRNA in hepatocellular carcinoma tissue were significantly higher than para-cancer liver tissue (P=0.000). ⑶The positive expression rate of TGFRβⅡmRNA in the tumor with membrace and cancer-embolus was significantly higher than those whithout tumor diaphragm and cancer-embolus（P＝0.019 and P＝0.039）. The positive expression rate of Smad4 mRNA with cancer-embolus was significantly higher than those without<WP=8>cancer-embolus（P＝0.031）. However, The positive expression rate of Smad7 mRNA with cancer-embolus was significantly lower than non-cancer-embolus type（P＝0.034）. No statistical correlation between expression change of TGF-β/SMAD molecule and patient’s age, size and differentiation of the tumor, AFP level of the patient’s serum and HBsAg were found (P>0.05).Concludes The mRNA expression of TGFβ1,TβRⅡ,Smad4, Smad7 were signifant different between cancer and corresponding para-caner liver tissue from patients with PHC . Furthermore, their expression has strong relationship with the important clinical indexs of PHC. All above indicated that TGF-β/SMAD signaling pathway may have important roles in the pathogenesis of PHC. It may be a helpful way for measuring prognosis for PHC to analysis the change of such componets of the signaling pathway.更多还原