循环中Hsa-miR-9、Hsa-miR-21、Hsa-miR-501的表达水平与非小细胞肺癌的相关性研究
发布时间：2018-09-04 07:57
【摘要】：[目的]1.检测非小细胞肺癌患者血清、血浆中miR-9、miR-21和miR-501的表达水平,探讨miR-9、miR-21和miR-501是否可能作为敏感性高、特异性强的非小细胞肺癌患者外周血miRNA的生物标志物。2.分析对比非小细胞肺癌患者、健康人血清与血浆中上述miRNA的表达差异,探索血清与血浆中的miRNA表达水平的差异。3.分析非小细胞肺癌患者血清、血浆中上述miRNA的表达水平与临床病理参数的关系并与目前临床上使用的血清肿瘤标志物对比,探索上述miRNA是否可用于监测非小细胞肺癌复发转移、评价治疗疗效及评估预后,并探讨上述miRNA能否成为宣威肺癌的特异性的生物标志物。[方法]1.收集符合入组标准的病人的病例资料,于患者入院后第二天清晨空腹静脉采血(抗凝血10ml、非抗凝血10ml),分别分离血清、血浆,储存于洁净离心管中置于-80℃储存备用,设置健康人为对照组。2.分别提取健康人组、非小细胞肺癌患者组血清、血浆中的miRNA,再采用qRT-PCR技术对miR-9、miR-21和miR-501进行扩增,检测上述miRNA的表达量,比较各组miR-9、miR-21和miR-501表达水平的高低。miR-9、miR-21和miR-501的相对表达量的公式为:2-△△CT。3.将所测患者miR-9、miR-21和miR-501按宣威与非宣威地区、男性与女性分组进行统计分析。4.分析血清、血浆中miR-9、miR-21和miR-501的表达水平与肺癌各临床病理参数及血清肿瘤标志物的水平的相关性。5.分别计算miR-9、miR-21和miR-501和血清肿瘤标志物CEA、CA125、CA153、CA199、CA242、CA724、FER、CYFRA21-1、NSE、SCC 的灵敏度和特异度,计算ROC曲线下面积。[结果]1.血清和血浆miR-9、miR-21在健康人、非小细胞肺癌患者中表达水平高,差异有统计学意义(P0.05), miR-501在健康人、非小细胞肺癌患者中表达差异没有统计学意义(P0.05)。2.血清miR-9表达水平健康组为:1.15±0.76,非小细胞肺癌组为:3.39±3.75;与健康人组相较,非小细胞肺癌组表达水平高于健康人组,两组差异具有统计学意义(P0.05)。血清miR-21表达水平健康组为:0.87±0.29,非小细胞肺癌组为:2.3±3.02;与健康人组相较,非小细胞肺癌组表达水平高于健康人组,两组差异具有统计学意义(P0.05)。血清miR-501表达水平健康组为:1.84±2.04,非小细胞肺癌组:2.30±3.02;与健康人组相较,非小细胞肺癌组表达水平高于健康人组,两组差异没有统计学意义(P0.05)。血浆miR-9表达水平健康组为:1.12±0.70,非小细胞肺癌组:3.41±3.73;与健康人组相较,非小细胞肺癌组表达水平高于健康人组,两组差异具有统计学意义(P0.05)。血浆miR-21表达水平健康组为:0.84±0.32,非小细胞肺癌组:2.37±3.04;与健康人组相较,非小细胞肺癌组表达水平高于健康人组,两组差异具有统计学意义(P0.05)。血浆miR-501表达水平健康组为:1.84±2.06,肺癌组:3.27±3.60;与健康人组相较,非小细胞肺癌组表达水平高于健康人组,两组差异没有统计学意义(P0.05)。3.对比非小细胞肺癌的血清和血浆中表达miR-9、miR-21、miR-501的水平,不论在非小细胞肺癌组还是健康组表达差异,P值均0.05,相关系数接近1,P0.001。4.分析外周血循环中miR-9和miR-21的表达水平与各临床病理参数有无相关性,提示miR-9和miR-21的表达高低与是否宣威籍不相关,miR-9和miR-21的表达与性别、年龄、TNM分期、转移均不相关(P0.05)。miR-21与病理类型不相关(P0.05), miR-9与病理类型存在相关性(P0.05)。5.外周血循环中miR-9水平升高与NSE,Cyfra21-1升高有关,(P0.05),外周血循环中miR-21水平升高与FER、Cyfra21-1、NSE、CA153升高有关,(P0.05)。6.检测非小细胞肺癌患者外周血循环中miR-9、miR-21的特异性和敏感性均没有完全优于肿瘤标志物 CEA、CA125、CA153、CA199、CA242、CA724、FER、CYFRA-12、NSE、SCC,其中miR-9的ROC曲线下面积达到0.75,具有诊断准确性中等。7.四种联合肿瘤标志物(miR-9, CEA, CA724, CYFRA21-1)特异性95.0%,敏感性82.0%, ROC曲线下面积为0.950,诊断准确性较高。[结论]1.miR-9和miR-21在非小细胞肺癌患者外周血循环中高表达,提示检测外周血循环中miR-9和miR-21的表达水平可用于非小细胞肺癌肿瘤的诊断,外周血循环中miR-9和miR-21具有成为非小细胞肺癌生物标志物的潜能。2.外周血循环中miRNAs表达在血清及血浆中对比没有差异。3.联合监测miR-9和CEA,CA724,CYFRA21-1的表达水平可以提高非小细胞肺癌的诊断准确率、降低假阳性率,更具有特异性和灵敏性。
[Abstract]:[Objective] 1. To detect the expression of microRNA-9, microRNA-21 and microRNA-501 in serum and plasma of patients with non-small cell lung cancer (NSCLC), and to explore the possibility of microRNA-9, microRNA-21 and microRNA-501 as biomarkers in peripheral blood of NSCLC patients with high sensitivity and specificity. To explore the expression of microRNAs in serum and plasma. 3. To analyze the relationship between the expression of microRNAs in serum and plasma and clinicopathological parameters in patients with non-small cell lung cancer, and to compare the expression of microRNAs with serum tumor markers currently used in clinic, to explore whether the microRNAs can be used to monitor the recurrence of non-small cell lung cancer. [Methods] 1. To collect the case data of patients who met the admission criteria and collect the fasting blood (anticoagulant 10ml, non-anticoagulant 10ml) in the morning after admission. Serum and plasma were separated and stored in Jie. MicroRNAs were extracted from serum and plasma of healthy people, non-small cell lung cancer patients, and amplified by qRT-PCR to detect the expression of microRNAs. The expression levels of microRNAs were compared among the three groups. The relative expression of microRNAs-21 and microRNAs-501 was formulated as follows: 2-delta CT.3. The expression levels of microRNAs-9, microRNAs-21 and microRNAs-501 in serum, plasma and clinical pathological parameters of lung cancer and serum tumor markers were analyzed. The sensitivity and specificity of serum tumor markers CEA, CA125, CA153, CA199, CA242, CA724, FER, CYFRA21-1, NSE and SCC were calculated respectively, and the area under ROC curve was calculated. [Results] 1. The expression levels of serum and plasma microRNAs-9, microRNA21 in healthy people and patients with non-small cell lung cancer were high, and the difference was statistically significant (P 0.05). There was no significant difference in the expression of - 501 between healthy and non-small cell lung cancer patients (P 0.05). 2. The expression level of serum microRNA-9 in healthy group was 1.15 [0.76] and non-small cell lung cancer group was 3.39 [3.75]. Compared with healthy group, the expression level of non-small cell lung cancer group was higher than that in healthy group, the difference was statistically significant (P 0.05). The expression level of serum microRNAs-501 in healthy group was 1.84 [2.04] and that in non-small cell lung cancer group was 2.30 [3.02] and that in healthy group was higher than that in healthy group (P 0.05). The expression level of serum microRNAs-501 in healthy group was 1.84 [2.04] and that in non-small cell lung cancer group was 2.30 [3.02] respectively. There was no significant difference between the two groups (P 0.05). The expression level of plasma microRNAs-9 in healthy group was 1.12 [0.70] and that in non-small cell lung cancer group was 3.41 [3.73]. Compared with healthy group, the expression level of plasma microRNAs-21 in non-small cell lung cancer group was higher than that in healthy group, the difference was statistically significant (P 0.05). The expression level of plasma microarray-501 in healthy group was 1.84 [2.06] and that in lung cancer group was 3.27 [3.60] and that in non-small cell lung cancer group was higher than that in healthy group (P 0.05). There was no significant difference between the two groups (P The expression of microRNA-9 and microRNA-21 was not correlated with sex, age, TNM stage and metastasis (P 0.05). MicroRNA-21 was not correlated with pathological type (P 0.05). MicroRNA-9 was correlated with pathological type (P 0.05). The level of microRNA-9 in peripheral blood circulation increased (P 0.05). The increased levels of microRNAs in peripheral blood circulation were associated with the increased levels of FER, Cyfra21-1, NSE and CA153, (P 0.05). 6. The specificity and sensitivity of detecting microRNAs-9 and microRNAs-21 in peripheral blood circulation of patients with non-small cell lung cancer were not completely superior to those of tumor markers CEA, CA125, CA153, CA199, CA242, CA724, FER, CYFRA-12, NSE, SC, CA242, CA724, FER, CYFRA-12, NSE, and SCE. Among them, the area under the ROC curve of microRNAs-9 was 0.75, and the diagnostic accuracy was moderate. 7. The specificity, sensitivity and area under the ROC curve of the four combined tumor markers (microRNAs-9, CEA, CA724, CYFRA21-1) were 95.0%, 82.0% and 0.950 respectively. The diagnostic accuracy of microRNAs-9 and microRNAs-21 was high in peripheral blood circulation of non-small cell lung cancer patients. Detecting the expression of microRNA-9 and microRNA-21 in peripheral blood circulation can be used for the diagnosis of non-small cell lung cancer. MicroRNA-9 and microRNA-21 in peripheral blood circulation have the potential to become biomarkers of non-small cell lung cancer. The expression level can improve the diagnostic accuracy of non-small cell lung cancer, reduce the false positive rate, and is more specific and sensitive.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
本文编号：2221471
[Abstract]:[Objective] 1. To detect the expression of microRNA-9, microRNA-21 and microRNA-501 in serum and plasma of patients with non-small cell lung cancer (NSCLC), and to explore the possibility of microRNA-9, microRNA-21 and microRNA-501 as biomarkers in peripheral blood of NSCLC patients with high sensitivity and specificity. To explore the expression of microRNAs in serum and plasma. 3. To analyze the relationship between the expression of microRNAs in serum and plasma and clinicopathological parameters in patients with non-small cell lung cancer, and to compare the expression of microRNAs with serum tumor markers currently used in clinic, to explore whether the microRNAs can be used to monitor the recurrence of non-small cell lung cancer. [Methods] 1. To collect the case data of patients who met the admission criteria and collect the fasting blood (anticoagulant 10ml, non-anticoagulant 10ml) in the morning after admission. Serum and plasma were separated and stored in Jie. MicroRNAs were extracted from serum and plasma of healthy people, non-small cell lung cancer patients, and amplified by qRT-PCR to detect the expression of microRNAs. The expression levels of microRNAs were compared among the three groups. The relative expression of microRNAs-21 and microRNAs-501 was formulated as follows: 2-delta CT.3. The expression levels of microRNAs-9, microRNAs-21 and microRNAs-501 in serum, plasma and clinical pathological parameters of lung cancer and serum tumor markers were analyzed. The sensitivity and specificity of serum tumor markers CEA, CA125, CA153, CA199, CA242, CA724, FER, CYFRA21-1, NSE and SCC were calculated respectively, and the area under ROC curve was calculated. [Results] 1. The expression levels of serum and plasma microRNAs-9, microRNA21 in healthy people and patients with non-small cell lung cancer were high, and the difference was statistically significant (P 0.05). There was no significant difference in the expression of - 501 between healthy and non-small cell lung cancer patients (P 0.05). 2. The expression level of serum microRNA-9 in healthy group was 1.15 [0.76] and non-small cell lung cancer group was 3.39 [3.75]. Compared with healthy group, the expression level of non-small cell lung cancer group was higher than that in healthy group, the difference was statistically significant (P 0.05). The expression level of serum microRNAs-501 in healthy group was 1.84 [2.04] and that in non-small cell lung cancer group was 2.30 [3.02] and that in healthy group was higher than that in healthy group (P 0.05). The expression level of serum microRNAs-501 in healthy group was 1.84 [2.04] and that in non-small cell lung cancer group was 2.30 [3.02] respectively. There was no significant difference between the two groups (P 0.05). The expression level of plasma microRNAs-9 in healthy group was 1.12 [0.70] and that in non-small cell lung cancer group was 3.41 [3.73]. Compared with healthy group, the expression level of plasma microRNAs-21 in non-small cell lung cancer group was higher than that in healthy group, the difference was statistically significant (P 0.05). The expression level of plasma microarray-501 in healthy group was 1.84 [2.06] and that in lung cancer group was 3.27 [3.60] and that in non-small cell lung cancer group was higher than that in healthy group (P 0.05). There was no significant difference between the two groups (P The expression of microRNA-9 and microRNA-21 was not correlated with sex, age, TNM stage and metastasis (P 0.05). MicroRNA-21 was not correlated with pathological type (P 0.05). MicroRNA-9 was correlated with pathological type (P 0.05). The level of microRNA-9 in peripheral blood circulation increased (P 0.05). The increased levels of microRNAs in peripheral blood circulation were associated with the increased levels of FER, Cyfra21-1, NSE and CA153, (P 0.05). 6. The specificity and sensitivity of detecting microRNAs-9 and microRNAs-21 in peripheral blood circulation of patients with non-small cell lung cancer were not completely superior to those of tumor markers CEA, CA125, CA153, CA199, CA242, CA724, FER, CYFRA-12, NSE, SC, CA242, CA724, FER, CYFRA-12, NSE, and SCE. Among them, the area under the ROC curve of microRNAs-9 was 0.75, and the diagnostic accuracy was moderate. 7. The specificity, sensitivity and area under the ROC curve of the four combined tumor markers (microRNAs-9, CEA, CA724, CYFRA21-1) were 95.0%, 82.0% and 0.950 respectively. The diagnostic accuracy of microRNAs-9 and microRNAs-21 was high in peripheral blood circulation of non-small cell lung cancer patients. Detecting the expression of microRNA-9 and microRNA-21 in peripheral blood circulation can be used for the diagnosis of non-small cell lung cancer. MicroRNA-9 and microRNA-21 in peripheral blood circulation have the potential to become biomarkers of non-small cell lung cancer. The expression level can improve the diagnostic accuracy of non-small cell lung cancer, reduce the false positive rate, and is more specific and sensitive.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
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