Expression of long non-coding RNA MALAT1, NEAT1 and NEAT2 in peripheral blood of tuberculosis patients
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摘要:
目的 分析肺结核患者与健康对照之间外周血单个核细胞(peripheral blood mononuclear cell, PBMC)中长链非编码RNA(long non-coding RNA, lncRNA)MALAT1、NEAT1和NEAT2的表达差异。 方法 利用定量逆转录聚合酶链式反应技术检测79例肺结核患者和82例健康对照PBMC中lncRNA的表达水平, 同时进一步分析lncRNA表达水平与肺结核患者部分临床特征、实验室指标之间的联系。 结果 肺结核患者PBMC中MALAT1、NEAT1的表达水平均高于健康对照, 差异有统计学意义(Z=-4.386, P < 0.001; Z=-10.175, P < 0.001);NEAT2在两组之间的表达差异无统计学意义(Z=-0.203, P=0.839)。LncRNA表达水平与肺结核患者部分临床特征、实验指标关联分析结果显示, 初治肺结核患者PBMC中NEAT2的表达水平高于复发肺结核患者, 而痰涂片阳性肺结核患者PBMC中NEAT2的表达水平低于痰涂片阴性患者, 差异均有统计学意义(均有P < 0.05);MALAT1水平与血沉含量之间呈负相关(rs=-0.256, P=0.034)。 结论 MALAT1、NEAT1在肺结核患者外周血中是异常表达的, 可能参与了肺结核的发病过程。 Abstract:Objective To analyze the differences in the expression levels of the lncRNA MALAT1, NEAT, NEAT2 in peripheral blood mononuclear cell(PBMC) from tuberculosis patients and healthy controls. Methods We detected the lncRNA expression levels in PBMC from 79 tuberculosis patients and 82 healthy controls by quantitative reverse transcription polymerase chain reaction, and analyzed the correlation between lncRNA expression levels and some clinical features and laboratory indicators in tuberculosis patients. Results The expression levels of MALAT1, NEAT1 in PBMC of tuberculosis patients were significantly higher than healthy controls(Z=-4.386, P < 0.001;Z=-10.175, P < 0.001). There was no significant difference in the expression of NEAT2 between tuberculosis patients and healthy controls(Z=-0.203, P=0.839). The correlation results of lncRNA levels and some clinical features, laboratory indicators in tuberculosis patients suggested that the NEAT2 level in PBMC of newly treated tuberculosis patients was higher than recurrent tuberculosis patients, while the NEAT2 level in PBMC of sputum smear positive tuberculosis patients was lower than that of sputum smear negative tuberculosis patients(all P < 0.05). There was a negative correlation between MALAT1 level and erythrocyte sedimentation rate(rs=-0.256, P=0.034). Conclusion MALAT1 and NEAT1 are abnormally expressed in PBMC of tuberculosis patients, and may be involved in the pathogenesis of pulmonary tuberculosis. -
Key words:
- Tuberculosis /
- Long non-coding RNA /
- Peripheral blood mononuclear cell
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表 1 肺结核患者与健康对照之间lncRNA表达水平比较
Table 1. Comparison of lncRNA expression levels between TB patients and healthy controls
目的基因 肺结核患者 健康对照 Z值 P值 MALAT1 [M(P25, P75)] 1.570(0.726, 2.237) 0.712(0.359, 1.356) -4.386 < 0.001 NEAT1 [M(P25, P75)] 4.948(3.538, 9.336) 0.479(0.249, 1.073) -10.175 < 0.001 NEAT2 [M(P25, P75)] 0.425(0.303, 0.621) 0.414(0.212, 0.816) -0.203 0.839 
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表 2 肺结核患者lncRNA表达水平与部分临床特征的关联
Table 2. The correlation between lncRNA expression level and some laboratory indexes in TB patients
分组 人数(人) MALAT1[M(P25, P75)] NEAT1[M(P25, P75)] NEAT2[M(P25, P75)] 初治患者 是 53 1.559(0.700, 2.307) 4.948(3.672, 9.312) 0.480(0.318, 0.700) 否 26 1.630(0.827, 2.174) 5.155(3.059, 9.434) 0.371(0.237, 0.518) Z值 -0.094 -0.720 -2.003 P值 0.925 0.472 0.045 耐药患者 是 17 1.559(0.746, 1.792) 4.871(2.725, 9.081) 0.350(0.262, 0.606) 否 62 1.604(0.713, 2.379) 5.206(3.567, 9.519) 0.468(0.309, 0.629) Z值 -0.632 -0.931 -1.229 P值 0.527 0.352 0.219 痰涂片结果a 阳性 31 1.570(0.737, 2.530) 5.858(3.142, 10.607) 0.361(0.251, 0.556) 阴性 42 1.650(0.713, 2.107) 4.749(3.542, 8.750) 0.486(0.315, 0.725) Z值 -0.446 -0.402 -2.065 P值 0.655 0.688 0.039 肺部结核病灶 单侧 21 1.751(0.653, 2.162) 4.223(3.178, 5.544) 0.489(0.311, 0.784) 双侧 58 1.569(0.778, 2.248) 5.700(3.542, 10.089) 0.385(0.286, 0.582) Z值 -0.033 -1.454 -1.487 P值 0.973 0.146 0.137 肺部空洞 有 27 1.570(0.675, 2.594) 5.923(3.178, 11.785) 0.420(0.280, 0.642) 无 52 1.573(0.729, 2.147) 4.644(3.560, 7.570) 0.427(0.310, 0.612) Z值 -0.589 -0.775 -0.217 P值 0.556 0.438 0.828 合并肺外结核 是 11 1.628(1.338, 2.594) 5.824(3.178, 7.776) 0.398(0.330, 0.575) 否 68 1.569(0.688, 2.221) 4.910(3.546, 9.631) 0.427(0.288, 0.637) Z值 -0.397 -0.085 -0.042 P值 0.692 0.932 0.966 合并肝功能损害 是 9 2.064(1.046, 2.455) 3.755(3.540, 7.173) 0.508(0.358, 0.646) 否 70 1.563(0.713, 2.190) 3.513(3.488, 9.815) 0.413(0.285, 0.627) Z值 -0.772 -0.941 -1.003 P值 0.440 0.347 0.316 合并糖尿病 是 16 1.402(0.429, 1.670) 5.337(2.480, 9.110) 0.398(0.288, 0.625) 否 63 1.690(0.909, 2.279) 4.948(3.557, 9.730) 0.430(0.303, 0.621) Z值 -1.610 -0.720 -0.281 P值 0.107 0.427 0.779 注:a表示部分患者资料缺失。
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表 3 肺结核患者lncRNA表达水平与部分实验室指标的相关性
Table 3. The correlation between lncRNA expression level and some laboratory indexes in TB patients
变量 人数(人) MALAT1 NEAT1 NEAT2 rs值 P值 rs值 P值 rs值 P值 血沉a 69 -0.256 0.034 0.042 0.734 -0.094 0.440 谷丙转氨酶 79 -0.019 0.871 -0.190 0.093 0.005 0.968 谷草转氨酶 79 -0.042 0.710 -0.068 0.553 -0.105 0.356 总胆红素 79 0.040 0.724 -0.161 0.155 -0.119 0.295 注:a表示部分患者资料缺失。
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