miR-10a-5p在急性髓系白血病患者中的表达特点及预后意义
发布时间：2018-08-30 10:36
【摘要】：目的:本单位血液科课题组前期研究发现急性髓系白血病(AML)患者与正常人的mi RNA表达谱存在显著差异,其中mi R-10a-5p高表达。本研究通过分析mi R-10a-5p在AML患者骨髓及血清中的表达情况,探讨mi R-10a-5p与AML临床生物学特征的关系及其预后意义,为mi R-10a-5p在AML的治疗及预后判断中的作用奠定实验基础和提供重要信息。方法:2009年12月至2014年10月收集苏州大学附属第三医院(常州市第一人民医院)收治的168例AML患者血清标本(初治患者108例,完全缓解患者39例,复发患者21例)及正常人血清对照25例;其中男117例,女51例,中位年龄51岁。2013年3月至2014年3月收集65例AML患者骨髓标本(初治患者36例,完全缓解患者15例,复发患者14例)及正常人骨髓对照14例;其中男41例,女24例,中位年龄51岁。同时购买急性早幼粒白血病细胞株HL-60及其阿霉素耐药细胞株HL-60/ADR;提取所有标本中总RNA,应用实时定量聚合酶链反应(RT-PCR)方法检测AML患者及对照组以及细胞株中mi R-10a-5p的表达情况;探讨其与AML临床、生物学特征的关系及其预后意义。结果:HL-60/ADR耐药株中mi R-10a-5p表达明显高于敏感株HL-60(6.8倍,p0.001);初治AML患者血清中mi R-10a-5p表达高于正常(p0.001),完全缓解组mi R-10a-5p表达低于初治组(p0.001),复发组的表达量又高于完全缓解组(p0.001),而完全缓解组的表达与正常组无明显统计学差异(p0.05);在AML患者骨髓细胞中mi R-10a-5p表达与血清标本出现同样的动态变化趋势;分析ROC(Receiver Operator Characteristic)曲线得出mi R-10a-5p诊断AML的灵敏度为79.6%,特异度为80.0%,ROC曲线下面积为0.831;分析骨髓单个核细胞mi R-10a-5p的表达与血清mi R-10a-5p表达的关系,发现两组标本中mi R-10a-5p的水平呈明显的正相关;分析血清mi R-10a-5p与临床指标的关系发现mi R-10a-5p与年龄(p=0.687)、性别(p=0.837)、白细胞计数(p=0.177)、血红蛋白浓度(p=0.441)、血小板计数(p=0.558)、骨髓原始细胞数(p=0.177)、脾肿大(p=0.558)、细胞遗传学(p=0.288)、NPM突变(p=0.319)、CD34阳性率(p=0.618)等临床特征无明显相关性。以mi R-10a-5p的中位数为界,将所有血清标本中初治AML患者分为高表达组和低表达组,分析初治患者经一疗程标准方案诱导化疗后,发现血清mi R-10a-5p高表达AML患者完全缓解率低于低表达AML患者(分别为38.8%,59.2%,p=0.043),而且血清mi R-10a-5p高表达AML患者总体生存率短于低表达AML患者(p=0.042)。结论:mi R-10a-5p在AML患者中普遍存在高表达,且在AML疾病发展过程中呈动态变化,与肿瘤负荷相关,高表达的mi R-10a-5p可能是AML预后不良的生物学标志之一。血清标本易于取得,血清mi R-10a-5p水平可以作为观测AML疾病发展的重要指标之一。
[Abstract]:Objective: in the previous study of our department of hematology, we found that there was significant difference in mi RNA expression profile between patients with acute myeloid leukemia (AML) and normal subjects, among which mi R-10a-5p was highly expressed. In this study, we analyzed the expression of mi R-10a-5p in bone marrow and serum of AML patients, and explored the relationship between mi R-10a-5p and clinical biological characteristics of AML and its prognostic significance. To lay the experimental foundation and provide important information for the role of mi R-10a-5p in the treatment and prognosis of AML. Methods: from December 2009 to October 2014, serum samples of 168 patients with AML were collected from the third affiliated Hospital of Suzhou University (the first people's Hospital of Changzhou). From March 2013 to March 2014, bone marrow specimens were collected from 65 patients with AML (36 patients with primary treatment and 15 patients with complete remission). There were 14 patients with recurrent bone marrow and 14 normal controls, including 41 males and 24 females with a median age of 51 years. At the same time, the expression of mi R-10a-5p was detected by real-time quantitative polymerase chain reaction (RT-PCR) in patients with acute promyelocytic leukemia (HL-60) and its adriamycin resistant cell line (HL-60/ADR;) by real-time quantitative polymerase chain reaction (RT-PCR). To explore the relationship between AML and clinical and biological characteristics and its prognostic significance. Results the expression of mi R-10a-5p was significantly higher in the% HL-60 / ADR resistant strain than in the sensitive strain HL-60 (6.8-fold p0.001), the expression of mi R-10a-5p in the newly treated AML patients was higher than that in the normal group (p0.001), the expression of mi R-10a-5p in the complete remission group was lower than that in the first treatment group (p0.001), and the expression of mi R-10a-5p in the relapsed group was higher than that in the complete remission group (p0.001). There was no significant difference in the expression of mi R-10a-5p between the complete remission group and the normal group (p0.05). The expression of mi R-10a-5p in the bone marrow cells of AML patients showed the same dynamic trend as the serum samples. The sensitivity and specificity of mi R-10a-5p in the diagnosis of AML were 79.6 and 0.831, respectively. The relationship between the expression of mi R-10a-5p in bone marrow mononuclear cells and the expression of serum mi R-10a-5p was found to be positively related to the level of mi R-10a-5p in the two groups. Analysis of the relationship between serum mi R-10a-5p and clinical indexes showed that the positive rate of CD34 in mi R-10a-5p and age (p0. 687), sex (p0. 837), white blood cell count (p0. 177), hemoglobin concentration (p0. 441), platelet count (p0. 558), bone marrow primordial cell count (p0. 177), splenomegaly (p0. 558), cytogenetics (p0. 288) mutation (p0. 319) and CD34 positive rate (p0. 618) were found. There was no significant correlation in clinical features. According to the median of mi R-10a-5p, the newly treated AML patients were divided into two groups: high expression group and low expression group. It was found that the complete remission rate of patients with high expression of mi R-10a-5p AML was lower than that of patients with low expression of AML (38.8% or 59.2%, respectively), and the overall survival rate of patients with high expression of AML in serum mi R-10a-5p was shorter than that of patients with low expression of AML (p0.042). Conclusion there is a high expression of R-10a-5p in AML patients, and it is a dynamic change during the development of AML. The high expression of mi R-10a-5p may be one of the biological markers of poor prognosis of AML. Serum samples are easy to be obtained, and serum mi R-10a-5p level can be used as an important index to observe the development of AML disease.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R733.71
本文编号：2212817
[Abstract]:Objective: in the previous study of our department of hematology, we found that there was significant difference in mi RNA expression profile between patients with acute myeloid leukemia (AML) and normal subjects, among which mi R-10a-5p was highly expressed. In this study, we analyzed the expression of mi R-10a-5p in bone marrow and serum of AML patients, and explored the relationship between mi R-10a-5p and clinical biological characteristics of AML and its prognostic significance. To lay the experimental foundation and provide important information for the role of mi R-10a-5p in the treatment and prognosis of AML. Methods: from December 2009 to October 2014, serum samples of 168 patients with AML were collected from the third affiliated Hospital of Suzhou University (the first people's Hospital of Changzhou). From March 2013 to March 2014, bone marrow specimens were collected from 65 patients with AML (36 patients with primary treatment and 15 patients with complete remission). There were 14 patients with recurrent bone marrow and 14 normal controls, including 41 males and 24 females with a median age of 51 years. At the same time, the expression of mi R-10a-5p was detected by real-time quantitative polymerase chain reaction (RT-PCR) in patients with acute promyelocytic leukemia (HL-60) and its adriamycin resistant cell line (HL-60/ADR;) by real-time quantitative polymerase chain reaction (RT-PCR). To explore the relationship between AML and clinical and biological characteristics and its prognostic significance. Results the expression of mi R-10a-5p was significantly higher in the% HL-60 / ADR resistant strain than in the sensitive strain HL-60 (6.8-fold p0.001), the expression of mi R-10a-5p in the newly treated AML patients was higher than that in the normal group (p0.001), the expression of mi R-10a-5p in the complete remission group was lower than that in the first treatment group (p0.001), and the expression of mi R-10a-5p in the relapsed group was higher than that in the complete remission group (p0.001). There was no significant difference in the expression of mi R-10a-5p between the complete remission group and the normal group (p0.05). The expression of mi R-10a-5p in the bone marrow cells of AML patients showed the same dynamic trend as the serum samples. The sensitivity and specificity of mi R-10a-5p in the diagnosis of AML were 79.6 and 0.831, respectively. The relationship between the expression of mi R-10a-5p in bone marrow mononuclear cells and the expression of serum mi R-10a-5p was found to be positively related to the level of mi R-10a-5p in the two groups. Analysis of the relationship between serum mi R-10a-5p and clinical indexes showed that the positive rate of CD34 in mi R-10a-5p and age (p0. 687), sex (p0. 837), white blood cell count (p0. 177), hemoglobin concentration (p0. 441), platelet count (p0. 558), bone marrow primordial cell count (p0. 177), splenomegaly (p0. 558), cytogenetics (p0. 288) mutation (p0. 319) and CD34 positive rate (p0. 618) were found. There was no significant correlation in clinical features. According to the median of mi R-10a-5p, the newly treated AML patients were divided into two groups: high expression group and low expression group. It was found that the complete remission rate of patients with high expression of mi R-10a-5p AML was lower than that of patients with low expression of AML (38.8% or 59.2%, respectively), and the overall survival rate of patients with high expression of AML in serum mi R-10a-5p was shorter than that of patients with low expression of AML (p0.042). Conclusion there is a high expression of R-10a-5p in AML patients, and it is a dynamic change during the development of AML. The high expression of mi R-10a-5p may be one of the biological markers of poor prognosis of AML. Serum samples are easy to be obtained, and serum mi R-10a-5p level can be used as an important index to observe the development of AML disease.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R733.71
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