腎透明細胞癌論文：ID4、E2F1在腎透明細胞癌中表達的意義及二者相互關(guān)系初步探討

1、腎透明細胞癌論文：ID4、E2F1在腎透明細胞癌中表達的意義及二者相互關(guān)系初步探討【中文摘要】研究分化抑制因子4(Inhibitor of DNA binding-4/or differentiation,Id4及核轉(zhuǎn)錄因子E2F1(Transcription factor E2F1,E2F1在腎透明細胞癌中的表達情況,探討二者在腎透明細胞癌發(fā)病機制中的作用,并分析其與腫瘤病理分級、臨床分期間的關(guān)系及二者在腎透明細胞癌中的表達是否存在相關(guān)性；以期為臨床腎透明細胞癌術(shù)后輔助靶向治療提供一種新的靶點選擇。方法：采用免疫組織化學SABC法檢測40例腎透明細胞癌、10例癌旁和10例非癌病變腎組織(正常

2、腎組織標本中Id4因子及E2F1因子的表達情況。實驗數(shù)據(jù)統(tǒng)計方法：計數(shù)非等級資料采用2檢驗或四格表Fisher確切概率法檢驗；計數(shù)等級資料采用Mann-Whitney U或Kruskal-Wallis H非參數(shù)秩和檢驗,相關(guān)性檢驗采用Spearman相關(guān)分析。結(jié)果：(1Id4、E2F1因子在腎透明細胞癌中的表達均明顯增高。在腎癌組中Id4因子陽性表達率為67.5%(27/40,較癌旁組的30%(3/10及非癌病變組(正常組的20%(2/10明顯增高；E2F1因子在腎癌組中陽性表達率為75%(30/40,癌旁組為40%(4/10,正常組為20%(2/10。Id4、E2F1兩者在腎透明細胞癌組織中

3、的陽性表達率分別與其它兩組進行比較,均有顯著差異。(2腎透明細胞癌中Id4、E2F1的表達與腫瘤病理分級無明顯相關(guān)。在腎透明細胞癌病理分級-中,雖然Id4因子隨腫瘤病理分級的增高,陽性表達率呈增加趨勢,分別為級58.3%(7/12、級70%(7/10、級70%(7/10、級75%(6/8,但四組之間差異無統(tǒng)計學意義。同樣的參照腎透明細胞癌病理分級方法,E2F1因子陽性表達率分別為級66.7%(8/12、級80%(8/10、級80%(8/10、級75%(6/8,四組間差異亦無統(tǒng)計學意義。(3Id4、E2F1兩者表達程度與腎透明細胞癌腫瘤臨床分期(cTNM分期無明顯相關(guān)。在早期腎癌(-期中Id4、

4、E2F1兩者陽性表達分別為65.5%(19/29及72.4%(21/29,而在晚期腎癌(-期中陽性表達率則分別為72.7%(8/11及81.8%(9/11。Id4和E2F1因子陽性表達率均隨腫瘤進展而呈增高趨勢,然而統(tǒng)計學分析顯示無顯著差異。(4Id4、E2F1在腎透明細胞癌組織中,共同呈陰性表達的有5例,呈陽性表達的有11例,呈強陽性表達的有9例,另有15例樣本中兩者陽性表達情況不相同；采用Spearman相關(guān)分析對數(shù)據(jù)進行處理,結(jié)果顯示二者在腎透明細胞癌中的表達存在正相關(guān)性。結(jié)論：Id4及E2F1因子在腎透明細胞癌發(fā)病機制中起重要作用,而且二者在腎透明細胞癌組織中的表達呈正相關(guān),或單獨或共

5、同對腎癌發(fā)病起促進作用；但二者表達程度與腎透明細胞癌的病理分級、臨床分期無明顯相關(guān)性,提示其對臨床腎癌患者預后評估價值有限；Id4、E2F1二者可為臨床腎癌患者術(shù)后輔助靶向治療提供一種新的選擇,是一種具有吸引力的抗腫瘤治療靶點?！居⑽恼?To investigate the expression and correlation of Inhibitor of DNA binding/or differentiation-4 (Id4 and Transcription factor E2F1(E2F1in the renal clear cell carcinoma(RCCC, and t

6、o 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

7、 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 with2 test or Fisher probabilities in 2x2 table; the grade materials

8、 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 I

9、d4 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.(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 p

10、athological grade, that was grade58.3%(7/12、grade70%(7/10、grade70%(7/10and 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、grade80%(8/10、grade80%(8/10and grade75%(6/8, there are also no sig

11、nificant difference between the four groups (P 0.05.(3. In the prophase renal cell carcinoma (-phase,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%(8/11and 81.8%(9/11 in the advanced stage (-phase. The expression of them were

12、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 pati

13、ents 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, P0.05.Conclusions:High expression of Id4 an E2F1 play an important role in pathogenesis of RCCC. And both of the expressions of them has

14、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,

15、 which may be provide a new option for renal carcinoma targeted therapy, are attractive targets for antitumor therapy.【關(guān)鍵詞】腎透明細胞癌 分化抑制因子4(Id4 核轉(zhuǎn)錄因子1(E2F1 免疫組織化學【英文關(guān)鍵詞】clear cell renal cell carcinoma transcription factor E2F1 Inhibitor of DNA binding/ or differentiation -4 immunohistochemistry【目錄】ID4、E2F1在腎透明細胞癌中表達的意義及二者相互關(guān)系初步探討摘要3-5ABSTRACT5-6第1章 引言9-12第2章 材料與方法12-162.1 實驗材料12-142.2 實驗方法142.3 結(jié)果判定14-152.4 統(tǒng)計學分析15-16第3章 結(jié)果16-203.1 Id4在腎透明細胞癌、癌旁、正常腎組織中的表達情況16-173.2 E2F1在腎透明細胞癌、癌旁、正常腎組織中的表達情況17-193.3 腎透明細胞癌中Id