C-MYC和MDM2蛋白在多发性骨髓瘤中的表达及其与临床分期的相关性

发布时间：2018-04-10 02:21

本文选题：C-myc蛋白　切入点：MDM2蛋白　出处：《郑州大学》2016年硕士论文

【摘要】：背景和目的多发性骨髓瘤(Multiple Myeloma,MM)是起源于骨髓中B淋巴细胞的单克隆浆细胞恶性肿瘤,是最常见发生于骨的淋巴造血系统肿瘤。目前其发病机制不清,无法治愈,尤其是临床分期越高,预后越差。因此探讨多发性骨髓瘤的发生发展机制,寻找其临床治疗的可能靶点及预后判断指标成为当前的研究热点。C-myc基因是MYC癌基因家族成员之一,其与细胞周期的调控密切相关。C-myc基因的异常表达在调节细胞的恶性转化、生长及分化中发挥重要作用。有关研究表明,在很多肿瘤,如淋巴瘤、乳腺癌、胃癌、结肠癌和头颈部肿瘤等,均有C-myc基因的扩增或过度表达。小鼠双微体基因(murine double minute 2,MDM2)是一种原癌基因,最初是从含有双微体的小鼠成纤维母细胞中克隆出的一个高度扩增的基因。MDM2通过激活E2F-1可以促进细胞G1期到S期的转变,通过抑制野生型P53的功能可以调控细胞的增殖、凋亡。其与许多恶性肿瘤的发生发展密切相关,如软组织肉瘤、骨肉瘤和胶质瘤等,因此,靶向作用于C-myc或MDM2及其相关基因有可能成为肿瘤治疗的有效途径之一。C-myc蛋白或MDM2蛋白在多发性骨髓瘤中表达的报道非常有限,联合检测C-myc蛋白和MDM2蛋白在多发性骨髓瘤组织的表达情况,目前尚未见相关报道。本研究应用免疫组化检测MDM2蛋白和C-myc蛋白在不同临床分期多发性骨髓瘤和非肿瘤骨髓组织的表达情况,以期了解二者在多发性骨髓瘤发生发展中的意义及其与临床分期的关系。方法1.应用免疫组织化学SP-9000三步法检测不同临床分期多发性骨髓瘤组织和非肿瘤骨髓组织中的C-myc蛋白及MDM2蛋白的表达情况。2.统计学分析:通过SPSS 21.0软件处理,对计数资料采用χ2检验,对于相关性分析采用Spearman等级相关分析。检验水准α=0.05。结果1.C-myc蛋白和MDM2蛋白在多发性骨髓瘤组织中的表达阳性率分别为71.7%、80.0%,在非肿瘤骨髓组织中的表达阳性率分别为10.0%、20.0%,两种蛋白在非肿瘤骨髓组织及多发性骨髓瘤组织的表达阳性率差异有统计学意义(P0.05)。2.C-myc蛋白和MDM2蛋白的表达与多发性骨髓瘤临床ISS分期呈正相关性(P0.05),与患者的年龄、性别无相关性(P0.05)。3.在多发性骨髓瘤中,C-myc蛋白和MDM2蛋白的表达呈正相关性(P0.05)。结论1.C-myc蛋白和MDM2蛋白在多发性骨髓瘤中高表达,其可能与多发性骨髓瘤的发生及临床分期有关,但与患者的年龄、性别无关。2.在多发性骨髓瘤中,C-myc蛋白和MDM2蛋白可能具有协同作用,共同促进肿瘤的发展。
[Abstract]:Background and objective multiple Myeloma (MMM) is a monoclonal plasmacyte malignant tumor originating from B lymphocytes in bone marrow. It is the most common lymphohemopoietic tumor occurring in bone.At present, its pathogenesis is not clear and can not be cured, especially the higher the clinical stage, the worse the prognosis.Therefore, to explore the mechanism of occurrence and development of multiple myeloma, to find out the possible targets of clinical treatment and prognostic indicators, has become a hot research topic. C-myc gene is one of the members of MYC oncogene family.It is closely related to the regulation of cell cycle. The abnormal expression of C-myc gene plays an important role in the regulation of malignant transformation, growth and differentiation of cells.Studies have shown that in many tumors, such as lymphoma, breast cancer, gastric cancer, colon cancer and head and neck tumors, there is amplification or overexpression of C-myc gene.Murine double minute 2 MDM2) is a proto-oncogene originally cloned from mouse fibroblasts containing double microbodies. MDM2 promotes the transition from G1 phase to S phase by activating E2F-1.The cell proliferation and apoptosis can be regulated by inhibiting the function of wild type p53.It is closely related to the occurrence and development of many malignant tumors, such as soft tissue sarcoma, osteosarcoma and glioma.Targeting C-myc or MDM2 and their associated genes may be one of the effective ways of tumor therapy. C-myc protein or MDM2 protein expression in multiple myeloma is very limited.The expression of C-myc protein and MDM2 protein in multiple myeloma tissues has not been reported.In this study, the expression of MDM2 protein and C-myc protein in multiple myeloma and non-tumor bone marrow tissues in different clinical stages were detected by immunohistochemistry in order to understand their significance in the development of multiple myeloma and their relationship with clinical staging.Method 1.Immunohistochemical SP-9000 three-step method was used to detect the expression of C-myc protein and MDM2 protein in multiple myeloma tissues and non-tumor bone marrow tissues in different clinical stages.Statistical analysis: SPSS 21.0 software was used to process the counting data, 蠂 2 test was used for counting data, and Spearman grade correlation analysis was used for correlation analysis.The test level is 伪 0. 05.Results the positive rates of 1.C-myc protein and MDM2 protein in multiple myeloma tissues were 71.7% and 80.0%, respectively, while those in non-tumor bone marrow tissues were 10.0% and 20.0%, respectively. The positive rates of the two proteins in non-tumor bone marrow tissues and multiple myeloma tissues were 10.0% and 20.0%, respectively.There was a significant difference in the positive rate of P0.05. 2.C-myc protein and MDM2 protein expression in patients with multiple myeloma, there was a positive correlation between the expression of P0.05 protein and the clinical ISS stage of multiple myeloma, and the expression of P0.05 protein was associated with the age of the patients.There was no correlation between sex and sex (P 0.05).The expression of C-myc protein and MDM2 protein in multiple myeloma was positively correlated with that of P0.05.Conclusion the high expression of 1.C-myc protein and MDM2 protein in multiple myeloma may be related to the occurrence and clinical stage of multiple myeloma, but it is not related to the age and sex of the patients.In multiple myeloma, C-myc protein and MDM2 protein may play a synergistic role in promoting the development of the tumor.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R733.3

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