循環(huán)中Hsa-miR-9、Hsa-miR-21、Hsa-miR-501的表達水平與非小細胞肺癌的相關性研究
發(fā)布時間：2018-09-04 07:57
【摘要】：[目的]1.檢測非小細胞肺癌患者血清、血漿中miR-9、miR-21和miR-501的表達水平,探討miR-9、miR-21和miR-501是否可能作為敏感性高、特異性強的非小細胞肺癌患者外周血miRNA的生物標志物。2.分析對比非小細胞肺癌患者、健康人血清與血漿中上述miRNA的表達差異,探索血清與血漿中的miRNA表達水平的差異。3.分析非小細胞肺癌患者血清、血漿中上述miRNA的表達水平與臨床病理參數(shù)的關系并與目前臨床上使用的血清腫瘤標志物對比,探索上述miRNA是否可用于監(jiān)測非小細胞肺癌復發(fā)轉移、評價治療療效及評估預后,并探討上述miRNA能否成為宣威肺癌的特異性的生物標志物。[方法]1.收集符合入組標準的病人的病例資料,于患者入院后第二天清晨空腹靜脈采血(抗凝血10ml、非抗凝血10ml),分別分離血清、血漿,儲存于潔凈離心管中置于-80℃儲存?zhèn)溆?設置健康人為對照組。2.分別提取健康人組、非小細胞肺癌患者組血清、血漿中的miRNA,再采用qRT-PCR技術對miR-9、miR-21和miR-501進行擴增,檢測上述miRNA的表達量,比較各組miR-9、miR-21和miR-501表達水平的高低。miR-9、miR-21和miR-501的相對表達量的公式為:2-△△CT。3.將所測患者miR-9、miR-21和miR-501按宣威與非宣威地區(qū)、男性與女性分組進行統(tǒng)計分析。4.分析血清、血漿中miR-9、miR-21和miR-501的表達水平與肺癌各臨床病理參數(shù)及血清腫瘤標志物的水平的相關性。5.分別計算miR-9、miR-21和miR-501和血清腫瘤標志物CEA、CA125、CA153、CA199、CA242、CA724、FER、CYFRA21-1、NSE、SCC 的靈敏度和特異度,計算ROC曲線下面積。[結果]1.血清和血漿miR-9、miR-21在健康人、非小細胞肺癌患者中表達水平高,差異有統(tǒng)計學意義(P0.05), miR-501在健康人、非小細胞肺癌患者中表達差異沒有統(tǒng)計學意義(P0.05)。2.血清miR-9表達水平健康組為:1.15±0.76,非小細胞肺癌組為:3.39±3.75;與健康人組相較,非小細胞肺癌組表達水平高于健康人組,兩組差異具有統(tǒng)計學意義(P0.05)。血清miR-21表達水平健康組為:0.87±0.29,非小細胞肺癌組為:2.3±3.02;與健康人組相較,非小細胞肺癌組表達水平高于健康人組,兩組差異具有統(tǒng)計學意義(P0.05)。血清miR-501表達水平健康組為:1.84±2.04,非小細胞肺癌組:2.30±3.02;與健康人組相較,非小細胞肺癌組表達水平高于健康人組,兩組差異沒有統(tǒng)計學意義(P0.05)。血漿miR-9表達水平健康組為:1.12±0.70,非小細胞肺癌組:3.41±3.73;與健康人組相較,非小細胞肺癌組表達水平高于健康人組,兩組差異具有統(tǒng)計學意義(P0.05)。血漿miR-21表達水平健康組為:0.84±0.32,非小細胞肺癌組:2.37±3.04;與健康人組相較,非小細胞肺癌組表達水平高于健康人組,兩組差異具有統(tǒng)計學意義(P0.05)。血漿miR-501表達水平健康組為:1.84±2.06,肺癌組:3.27±3.60;與健康人組相較,非小細胞肺癌組表達水平高于健康人組,兩組差異沒有統(tǒng)計學意義(P0.05)。3.對比非小細胞肺癌的血清和血漿中表達miR-9、miR-21、miR-501的水平,不論在非小細胞肺癌組還是健康組表達差異,P值均0.05,相關系數(shù)接近1,P0.001。4.分析外周血循環(huán)中miR-9和miR-21的表達水平與各臨床病理參數(shù)有無相關性,提示miR-9和miR-21的表達高低與是否宣威籍不相關,miR-9和miR-21的表達與性別、年齡、TNM分期、轉移均不相關(P0.05)。miR-21與病理類型不相關(P0.05), miR-9與病理類型存在相關性(P0.05)。5.外周血循環(huán)中miR-9水平升高與NSE,Cyfra21-1升高有關,(P0.05),外周血循環(huán)中miR-21水平升高與FER、Cyfra21-1、NSE、CA153升高有關,(P0.05)。6.檢測非小細胞肺癌患者外周血循環(huán)中miR-9、miR-21的特異性和敏感性均沒有完全優(yōu)于腫瘤標志物 CEA、CA125、CA153、CA199、CA242、CA724、FER、CYFRA-12、NSE、SCC,其中miR-9的ROC曲線下面積達到0.75,具有診斷準確性中等。7.四種聯(lián)合腫瘤標志物(miR-9, CEA, CA724, CYFRA21-1)特異性95.0%,敏感性82.0%, ROC曲線下面積為0.950,診斷準確性較高。[結論]1.miR-9和miR-21在非小細胞肺癌患者外周血循環(huán)中高表達,提示檢測外周血循環(huán)中miR-9和miR-21的表達水平可用于非小細胞肺癌腫瘤的診斷,外周血循環(huán)中miR-9和miR-21具有成為非小細胞肺癌生物標志物的潛能。2.外周血循環(huán)中miRNAs表達在血清及血漿中對比沒有差異。3.聯(lián)合監(jiān)測miR-9和CEA,CA724,CYFRA21-1的表達水平可以提高非小細胞肺癌的診斷準確率、降低假陽性率,更具有特異性和靈敏性。
[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.
【學位授予單位】：昆明醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2
本文編號：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.
【學位授予單位】：昆明醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R734.2
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