MCM2与Survivin在预测局部晚期宫颈癌新辅助化疗疗效中的作用

发布时间：2018-02-25 04:25

本文关键词： 微小染色体维持蛋白2 生长素宫颈癌新辅助化疗　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:微小染色体维持蛋白2(Minichromosome maintenance protein 2,MCM2)与Survivin可以促进宫颈癌细胞的增殖,抑制其凋亡,因此两者在宫颈癌的进展过程中有一定的作用。通过检测局部晚期宫颈癌患者新辅助化疗(Neoadjuvant chemotherapy,NACT)前后MCM2与Survivin的表达水平变化,了解NACT对其表达的影响。探讨局部晚期宫颈癌NACT前MCM2、Survivin的相关性及其与NACT疗效的相关性,旨在做到预见性化疗,为有效评估NACT疗效提供敏感性的预测指标。方法:选取2015年3月-2016年7月山西医科大学第二医院妇科门诊经阴道镜活检确诊为局部晚期宫颈癌的患者30例。阴道镜检查后用活检钳钳夹宫颈癌组织,用0.9%Nacl冲洗组织血渍,铝箔纸将其包裹,并存入液氮罐。入选患者均无化疗禁忌症,且未接受过手术及放射治疗,在患者签署知情同意书的情况下给予2个疗程的TC方案(紫杉醇+卡铂)化疗,后行宫颈癌根治术时再次留取相应患者的新鲜宫颈癌组织,存放入液氮罐。提取宫颈癌组织的总RNA和总蛋白,采用Real-time q PCR和Western blot方法检测NACT前后MCM2和Survivin的m RNA和蛋白表达水平的变化。结果:1.局部晚期宫颈癌患者行NACT后肿瘤直径明显缩小,由化疗前的(42.43±5.90)mm缩小至(24.29±1.60)mm(P0.05),临床总有效率为83.3%。2.局部晚期宫颈癌患者行NACT后MCM2与Survivin的表达较化疗前均降低。RT-q PCR检测化疗后MCM2与Survivin的m RNA相对表达量为0.62±0.11、0.86±0.13,与化疗前的m RNA表达量1.31±0.23、1.28±0.19相比显著降低(P0.05)。Western blot检测化疗后MCM2与Survivin的蛋白相对表达量为0.18±0.02、0.19±0.02,与化疗前的蛋白相对表达量0.90±0.02、0.49±0.03相比显著降低(P0.05)。3.局部晚期宫颈癌患者NACT前有效组中MCM2与Survivin的表达均高于无效组。RT-q PCR检测有效组中MCM2与Survivin的m RNA相对表达量为1.52±0.26、1.45±0.21,相比无效组中的m RNA表达量0.40±0.06、0.40±0.03明显增高(P0.05)。Western blot检测有效组中MCM2与Survivin的蛋白相对表达量为0.94±0.01、0.52±0.02,相比与无效组中的蛋白表达量0.75±0.02、0.34±0.01明显增高(P0.05)。4.NACT前MCM2与Survivin在局部晚期宫颈癌中的表达经Pearson积差相关系数分析发现具有正相关性,相关系数r为0.876。结论:1.局部晚期宫颈癌中MCM2和Survivin在患者行NACT后表达水平明显低于化疗前,提示其可能作为评估和预测NACT对宫颈癌患者作用的有效筛选指标。2.在局部晚期宫颈癌疗效有效组中MCM2、Survivin有高表达,提示其表达程度有助于评判患者对行NACT的敏感性。
[Abstract]:Objective: minichromosome maintenance protein 2 (Minichromosome maintenance 2 protein, MCM2) and Survivin can promote the proliferation of cervical cancer cells, inhibition of apoptosis, so they have a certain role in the progression of cervical cancer. Neoadjuvant chemotherapy for locally advanced cervical cancer patients were detected by (Neoadjuvant chemotherapy, NACT) and the changes of MCM2 expression level before and after Survivin, to understand the impact of NACT on the expression of locally advanced cervical cancer before NACT MCM2, the correlation of Survivin and its correlation with the efficacy of NACT, aiming at the predictability of chemotherapy, provide a predictor of sensitivity to effectively assess the efficacy of NACT. Methods: from March 2015 July -2016 Shanxi Medical University second hospital gynecology clinic by colposcopy biopsy for 30 cases of locally advanced cervical cancer. Patients with cervical cancer tissue forceps colposcopy, washed by 0.9%Nacl Tissue blood, foil wrapped it, and stored in liquid nitrogen tank. All patients had no chemotherapy contraindications, and did not receive surgery and radiotherapy, TC regimen in patients signed informed consent under the condition of given 2 courses (paclitaxel + carboplatin) chemotherapy after radical resection of cervical cancer specimens from the corresponding again patients with fresh cervical cancer, stored in liquid nitrogen tank. Total RNA was extracted from cervical carcinoma tissue and total protein, using Real-time Q PCR and Western blot method to detect the NACT before and after M RNA and MCM2 protein and Survivin expression. Results: 1. patients with late local cervical carcinoma in stage NACT tumor diameter significantly decreased after. After chemotherapy (42.43 + 5.90) mm was reduced to (24.29 + 1.60) mm (P0.05), the total effective rate was 83.3%.2. in patients with locally advanced cervical cancer after NACT the expression of MCM2 and Survivin were lower than before chemotherapy,.RT-q PCR and Survi MCM2 test measured after chemotherapy M RNA the relative expression of VIN was 0.62 + 0.11,0.86 + 0.13, M Expression and RNA before chemotherapy was 1.31 + 0.23,1.28 + 0.19 was significantly lower than (P0.05).Western blot detection of MCM2 after chemotherapy and Survivin protein expression was 0.18 + 0.02,0.19 + 0.02, and the protein expression before chemotherapy was 0.90 + 0.02,0.49 + 0.03 (P0.05) was significantly lower than the expression of MCM2 Survivin and.3. NACT in patients with locally advanced cervical cancer before the effective group were higher than in M RNA group Survivin.RT-q PCR invalid MCM2 and effective detection of relative expression level was 1.52 + 0.26,1.45 + 0.21, RNA group compared to invalid m expression in 0.40 + 0.06,0.40 + 0.03 significantly increased (P0.05) and MCM2 Survivin.Western blot detection group in protein relative expression was 0.94 + 0.01,0.52 + 0.02, compared with the expression of the protein in the amount of invalid group 0.75 + 0.02,0.34 + 0.01 was significantly higher (P0.05).4.NACT MCM2 and Su The expression of rvivin in locally advanced cervical cancer by Pearson correlation coefficient analysis showed a positive correlation, the correlation coefficient r was 0.876. conclusion: MCM2 and Survivin 1. in locally advanced cervical cancer in patients after NACT expression levels were significantly lower than before chemotherapy, suggesting that it may be as the assessment and prediction of MCM2.2. effective screening index of patients with cervical cancer NACT in locally advanced cervical cancer group, Survivin high expression, suggesting that its expression level is helpful to judge the patient sensitivity to NACT.

【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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