Sox2、Sall4、Klf4及Wnt信号通路蛋白β-catenin在子宫内膜样腺癌中的表达及其相关性分析

发布时间：2019-04-11 07:11

【摘要】：目的:1.探讨Sox2、Sall4、Klf4和β-catenin在不同宫内膜组织中的表达及其临床意义,并分析几者在子宫内膜样腺癌组织中表达的相关性,为进一步探讨子宫内膜癌发生机制提供理论依据。2.探索Sox2、Sall4、Klf4和β-catenin与子宫内膜样腺癌临床病理特征的关系,为该肿瘤早期的诊断、治疗及预后监测提供较好的理论基础。3.通过细胞学实验,观察经紫杉醇处理前后Sox2、Sall4、Klf4和β-catenin在细胞株(Ishikawa细胞和HEC-1A细胞)表达情况的变化,探讨紫杉醇药物对子宫内膜样腺癌的化疗效果,为该肿瘤进一步靶向治疗提供理论依据。方法:1.收集宫内膜组织140例,分别为正常增生期子宫内膜30例,增生性子宫内膜40例(不伴不典型性的增生和不典型增生各20例),子宫内膜样腺癌70例(高分化癌30例,中、低分化癌各20例)。采用免疫组织化学MaxVisionTM法检测Sox2、Sall4、Klf4与β-catenin表达水平。2.采用CCK-8检测不同浓度紫杉醇作用于Ishikawa、HEC-1A细胞后细胞的增殖抑制率。3.Western blot方法检测药物作用前后Sox2、Sall4、Klf4和β-catenin表达水平变化,探讨紫杉醇药物对子宫内膜样腺癌的疗效。4.统计学方法:应用SPSS19.0软件对实验结果数据进行统计分析,视P0.05为具有统计学差异。结果:1.在正常组织及增生性子宫内膜组织中Sox2、Sall4、Klf4基本不表达,β-catenin于宫内膜腺体细胞膜上高表达,sox2、sall4、klf4与β-catenin在正常子宫内膜与增生性子宫内膜中的表达无明显差异(p0.05)。同正常子宫内膜和增生性子宫内膜相比,子宫内膜样腺癌组织中sox2、sall4、klf4表达升高,β-catenin表达降低,差异具有统计学意义(p均小于0.05)。2.sox2、sall4、klf4与β-catenin的表达与子宫内膜样腺癌的病理组织学分级、浸润深度及淋巴结转移有关(p0.05),但与患者年龄无关(p0.05)。3.sox2、sall4、klf4三者分别与β-catenin在子宫内膜样腺癌中的表达呈负相关(β-catenin与sox2:r=-0.685,p0.05;β-catenin与sall4:r=-0.453,p0.05;β-catenin与klf4:r=-0.438,p0.05),sox2、sall4、klf4三者相互之间的表达均呈正相关(sox2与sall4:r=0.456,p0.05;sox2与klf4:r=0.470,p0.05;sall4与klf4:r=0.578,p0.05)。4.1μg/ml、5μg/ml、10μg/ml、20μg/ml、100μg/ml浓度紫杉醇对ishikawa和hec-1a细胞均有明显抑制作用,浓度越高抑制率越高。5.westernblot检测结果发现ishikawa、hec-1a细胞中sox2、sall4、klf4在紫杉醇作用后表达均明显升高,β-catenin的表达在紫杉醇作用前后无明显变化。结论:1.sox2、sall4、klf4与β-catenin的表达与子宫内膜样腺癌密切相关,是肿瘤相关因子。2.sox2、sall4、klf4与β-catenin表达水平与子宫内膜样腺癌临床病理因素密切相关,提示它们参与诱导子宫内膜样腺癌的发生发展,其表达情况可为该肿瘤的治疗方法的选择和有效的预后监测提供有效依据。3.Sox2、Sall4、Klf4及β-catenin在子宫内膜样腺癌中的表达高度相关,提示Sox2、Sall4、Klf4三者存在相互作用,可能是该肿瘤的肿瘤干细胞因子,并与Wnt/β-catenin信号通路相关,共同推动子宫内膜样腺癌的发生发展。4.单用紫杉醇β-catenin表达无变化,Sox2、Sall4、Klf4三者表达水平反而升高,推测细胞可能产生耐药性,单用化疗药物对子宫内膜样腺癌治疗效果可能不佳,易出现肿瘤复发和转移。
[Abstract]:Objective:1. The expression and clinical significance of Sox2, Sall4, Klf4 and Catenin in different endometrial tissues were discussed. The correlation between the expression of Sox 2, Sall4, Klf4 and Catenin in the tissue of endometrial adenocarcinoma was analyzed, and the theoretical basis for further study of the mechanism of endometrial carcinoma was also discussed. To explore the relationship between Sox2, Sall4, Klf4 and the clinicopathological features of endometrial-like adenocarcinoma, and provide a good theoretical basis for the early diagnosis, treatment and prognosis of the tumor. The changes of the expression of Sox2, Sall4, Klf4 and Catenin in cell lines (Ishikawa cells and HEC-1A cells) before and after the treatment with paclitaxel were observed by the cytological experiments, and the effect of the paclitaxel drug on the endometrial adenocarcinoma was discussed, and the theoretical basis for further targeted therapy of the tumor was also discussed. Method:1. 140 cases of endometrial tissue were collected, including 30 cases of normal proliferative endometrium,40 cases of hyperplastic endometrium (20 cases of atypical hyperplasia and atypical hyperplasia),70 cases of endometrial adenocarcinoma (30 cases of high differentiation cancer,20 cases of medium and low differentiated cancer). The expression level of Sox2, Sall4, Klf4 and HCO3-catenin was detected by using the immunohistochemical method of MaxVisionTM. The effect of paclitaxel on endometrial adenocarcinoma was studied by using CCK-8 to detect the inhibitory rate of paclitaxel on the cells after Ishikawa and HEC-1A cells. Statistical method: SPSS 19.0 software was used to carry out the statistical analysis of the data of the experiment, and the statistical difference was observed according to the P0.05. Results:1. The expression of Sox 2, Sall4 and Klf4 in the normal tissues and the hyperplastic endometrial tissues was not significant, and the expression of sox2, sall4, klf4 in the normal endometrium and the proliferative endometrium was not significantly different (p0.05). In comparison with that normal endometrium and the proliferative endometrium, the expression of sox2, sall4, klf4 in the tissue of the endometrial-like adenocarcinoma was increased, the expression of HCO3-catinin was decreased, and the difference was statistically significant (p <0.05). The expression of klf4 and n-catenin was related to the pathological grade, invasion depth and lymph node metastasis (p0.05), but not related to the age of the patient (p0.05).3. sox2, sall4, and klf4 were negatively correlated with the expression of n-catenin in the endometrioid adenocarcinoma (P-catenin and sox2: r =-0.685, p0.05; The expression of HCO3-catenin and sall4: r =-0.453, p0.05; t-catenin and klf4: r =-0.438, p0.05), sox2, sall4, and klf4 were positively correlated with each other (sox2 and sall4: r = 0.456, p0.05; splay 4 and klf4: r = 0.470, p0.05). 4.1. mu.g/ ml,5. mu.g/ ml,10. mu.g/ ml,20. mu.g/ ml, The results of western blot showed that the expression of sox2, sall4 and klf4 in shikawa and hc-1a cells increased significantly after the effect of paclitaxel. Conclusion:1. The expression of sox2, sall4, klf4 and n-catenin is closely related to the endometrial adenocarcinoma, and it is a tumor-related factor. the expression condition can provide an effective basis for the selection of the treatment method of the tumor and the effective prognosis monitoring,3. the expression level of the Sox2, the Sall4, the Klf4 and the n-catenin in the endometrial-like adenocarcinoma is highly correlated, and the interaction of the Sox 2, the Sall4 and the Klf4 can be the tumor stem cell factor of the tumor, It is associated with the Wnt/ P-cattenin signaling pathway to promote the development of endometrial-like adenocarcinoma. The expression of Taxol-catenin alone increased, and the expression level of Sox2, Sall4 and Klf4 increased, and it was suggested that the cell might be resistant to drug resistance. The effect of chemotherapy alone on the treatment of endometrial-like adenocarcinoma may not be good, and the recurrence and metastasis of the tumor can be easily.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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