【作者】 吴剑；

【导师】 史子敏；

【作者基本信息】 南昌大学 ， 外科学， 2011， 硕士

【摘要】 目的：研究分化抑制因子4(Inhibitor of DNA binding-4/or differentiation,Id4)及核转录因子E2F1(Transcription factor E2F1,E2F1)在肾透明细胞癌中的表达情况,探讨二者在肾透明细胞癌发病机制中的作用,并分析其与肿瘤病理分级、临床分期间的关系及二者在肾透明细胞癌中的表达是否存在相关性；以期为临床肾透明细胞癌术后辅助靶向治疗提供一种新的靶点选择。方法：采用免疫组织化学SABC法检测40例肾透明细胞癌、10例癌旁和10例非癌病变肾组织(正常肾组织)标本中Id4因子及E2F1因子的表达情况。实验数据统计方法：计数非等级资料采用χ2检验或四格表Fisher确切概率法检验；计数等级资料采用Mann-Whitney U或Kruskal-Wallis H非参数秩和检验,相关性检验采用Spearman相关分析。结果：(1)Id4、E2F1因子在肾透明细胞癌中的表达均明显增高。在肾癌组中Id4因子阳性表达率为67.5%(27/40),较癌旁组的30%(3/10)及非癌病变组(正常组)的20%(2/10)明显增高；E2F1因子在肾癌组中阳性表达率为75%(30/40),癌旁组为40%(4/10),正常组为20%(2/10)。Id4、E2F1两者在肾透明细胞癌组织中的阳性表达率分别与其它两组进行比较,均有显著差异(P<0.05),而癌旁组和正常组两组间比较无明显差异(P>0.05)。(2)肾透明细胞癌中Id4、E2F1的表达与肿瘤病理分级无明显相关。在肾透明细胞癌病理分级Ⅰ-Ⅳ中,虽然Id4因子随肿瘤病理分级的增高,阳性表达率呈增加趋势,分别为Ⅰ级58.3%(7/12)、Ⅱ级70%(7/10)、Ⅲ级70%(7/10)、Ⅳ级75%(6/8),但四组之间差异无统计学意义(P>0.05)。同样的参照肾透明细胞癌病理分级方法,E2F1因子阳性表达率分别为Ⅰ级66.7%(8/12)、Ⅱ级80%(8/10)、Ⅲ级80%(8/10)、Ⅳ级75%(6/8),四组间差异亦无统计学意义(P>0.05)。(3)Id4、E2F1两者表达程度与肾透明细胞癌肿瘤临床分期(cTNM分期)无明显相关。在早期肾癌(Ⅰ-Ⅱ期)中Id4、E2F1两者阳性表达分别为65.5%(19/29)及72.4%(21/29),而在晚期肾癌(Ⅲ-Ⅳ期)中阳性表达率则分别为72.7%(8/11)及81.8%(9/11)。Id4和E2F1因子阳性表达率均随肿瘤进展而呈增高趋势,然而统计学分析显示无显著差异(P>0.05)。(4)Id4、E2F1在肾透明细胞癌组织中,共同呈阴性表达的有5例,呈阳性表达的有11例,呈强阳性表达的有9例,另有15例样本中两者阳性表达情况不相同；采用Spearman相关分析对数据进行处理,结果显示二者在肾透明细胞癌中的表达存在正相关性(r=0.588,P<0.05)。结论：Id4及E2F1因子在肾透明细胞癌发病机制中起重要作用,而且二者在肾透明细胞癌组织中的表达呈正相关,或单独或共同对肾癌发病起促进作用；但二者表达程度与肾透明细胞癌的病理分级、临床分期无明显相关性,提示其对临床肾癌患者预后评估价值有限；Id4、E2F1二者可为临床肾癌患者术后辅助靶向治疗提供一种新的选择,是一种具有吸引力的抗肿瘤治疗靶点。更多还原

【Abstract】 Objective:To investigate the expression and correlation of Inhibitor of DNA binding/or differentiation-4 (Id4) and Transcription factor E2F1(E2F1)in the renal clear cell carcinoma(RCCC), and to explore the role of them in the pathogenesis of RCCC. we expected that the study will help us to elucidate whether the two involved in pathologic grading of cancer and clinical stage, and to provide novel therapeutic targets for clinical treatment of renal cell carcinoma(RCC).Methods:The expression of Id4 and E2F1 were detected with immunohistochemical SABC methods in 40 cases of RCCC,10 cases of adjacent tissues and 10 cases of normal renal tissues. The statistical analysis methods of data:the count materials were evaluated withχ2 test or Fisher probabilities in 2x2 table; the grade materials were evaluated with nonparametric rank sum test (Mann-Whitney U test or Kruskal-Wallis Htest);and the correlation using Spearman rank correlation analysis.Results:(1). The expression of Id4 and E2F1 in the RCCC were Significantly higher than adjacent tissues and normal tissues. The positive rate of Id4 in RCCC group was 67.5%(27/40), compared with the adjacent group 30%(3/10) and normal group 20% (2/10) was significantly higher(P<0.05). Moreover, the positive rate of E2F1 in the there groups were 75%(30/40)in the RCCC group,40%(4/10) in the adjacent group and 20%(2/10) in the normal group. Both of the positive rates of Id4 and E2F1 in the RCCC group compared with the other two groups were significantly different (P<0.05), while the adjacent group and the control group have no significant difference between the two groups (P> 0.05).(2). There is no significant correlation between the expression of Id4、E2F1 and the pathologic grading of cancer. The positive rate of Id4 was increased with higher pathological grade, that was gradeⅠ58.3%(7/12)、gradeⅡ70%(7/10、gradeⅢ70%(7/10)and grade IV75%(6/8), but there are no significant correlation between them (P> 0.05). At the same time, the positive expression rate of E2F1 were grade I 66.7%(8/12)、gradeⅡ80%(8/10)、gradeⅢ80%(8/10)and gradeⅣ75%(6/8), there are also no significant difference between the four groups (P> 0.05).(3). In the prophase renal cell carcinoma (Ⅰ-Ⅱphase),the positive rates of Id4、E2F1 were 65.5%(19/29) and 72.4%(21/29). At the same time, the positive rates of them were 72.7%(8/11)and 81.8%(9/11) in the advanced stage (Ⅲ-Ⅳphase). The expression of them were increased with higher clinical TNM staging(cTNM), but it is Statistically insignificant (P> 0.05).(4). In the clear renal cell carcinoma, the expressions of Id4, E2F1, that was common negative in 5 cases, while positive expression in 11 cases, and strong positive expression in 9 patients.Another 15 patients have a different expression. Spearman correlation analysis showed that both of them existed a positive correlation in the clear cell renal carcinoma(r=0.588, P<0.05).Conclusions:High expression of Id4 an E2F1 play an important role in pathogenesis of RCCC. And both of the expressions of them has a positive correlation, maybe have a synergetic effect to promote tumorigenesis,or promote tumorigenesis alone. However, there is no significant correlation between the high expression and tumor grade, clinical stage. It is less value for the evaluation of tumor prognostic in patients. Id4 and E2F1, which may be provide a new option for renal carcinoma targeted therapy, are attractive targets for antitumor therapy.更多还原