急性髓系白血病患者血浆lncRNA同源盒基因A-反义链2和miR-124-3p表达及其与预后的关系

Expressions of lncRNA HOXA-AS2 and miR-124-3p and relationships with prognosis of patients with acute myeloid leukemia

目的观察急性髓系白血病(acute myeloid leukemia,AML)患者血浆长链非编码RNA(long non-coding RNA,lncRNA)同源盒基因A-反义链2(homeobox gene A-antisense strand 2,HOXA-AS2)、miR-124-3p的表达情况,探讨其与临床病理特征及预后的关系。方法AML患者116例为AML组,均根据AML分型给予标准化疗方案治疗。同期体检健康者116例为对照组。采用实时荧光定量PCR法检测AML组入院时2组血浆lncRNA HOXA-AS2、miR-124-3p相对表达量;比较不同临床病理特征AML患者血浆lncRNA HOXA-AS2、miR-124-3p相对表达量;采用Pearson相关性分析AML患者血浆lncRNA HOXA-AS2与miR-124-3p相对表达量的相关性。AML患者根据lncRNA HOXA-AS2、miR-124-3p相对表达量均值分为lncRNA HOXA-AS2高表达组(lncRNA HOXA-AS2相对表达量≥3.54)62例和lncRNA HOXA-AS2低表达组(lncRNA HOXA-AS2相对表达量<3.54)54例、miR-124-3p高表达组(miR-124-3p相对表达量≥0.99)55例和miR-124-3p低表达组(miR-124-3p相对表达量<0.99)61例。随访3年,采用Kaplan-Meier生存曲线分析lncRNA HOXA-AS2与miR-124-3p高、低表达组患者3年总生存率;采用多因素Cox回归分析AML患者预后不良的影响因素。结果AML组血浆lncRNA HOXA-AS2相对表达量(3.54±0.98)高于对照组(0.82±0.25)(t=28.942,P<0.001),miR-124-3p相对表达量(0.99±0.37)低于对照组(3.47±1.29)(t=—19.945,P<0.001)。AML患者白细胞计数≥30×10^(9)/L、骨髓原始细胞比率≥70%者lncRNA HOXA-AS2相对表达量(3.76±0.87、3.75±0.89)分别高于白细胞计数<30×10^(9)/L(3.33±1.04)、骨髓原始细胞比率<70%者(3.24±1.03)(t=2.406,P=0.018;t=2.886,P=0.005),miR-124-3p相对表达量(0.88±0.35、0.91±0.36)分别低于白细胞计数<30×10^(9)/L(1.09±0.37)、骨髓原始细胞比率<70%者(1.10±0.37)(t=-3.171,P=0.002;t=-2.776,P=0.006)。预后危险度分层高危者lncRNA HOXA-AS2相对表达量高于中危、低危者(P<0.05),中危者高于低危者(P<0.05);高危者miR-124-3p相对表达量低于中危、低危者(P<0.05),中危者低于低危者(P<0.05)。AML患者血浆lncRNA HOXA-AS2与miR-124-3p相对表达量呈负相关(r=—0.684,P<0.001)。lncRNA HOXA-AS2高表达组3年总生存率(27.42%)低于lncRNA HOXA-AS2低表达组(62.96%)(χ^(2)=9.646,P=0.002),miR-124-3p低表达组3年总生存率(31.15%)低于miR-124-3p高表达组(58.18%)(χ^(2)=10.318,P=0.001)。白细胞计数≥30×10^(9)/L(HR=2.249,95%CI:1.298~3.895,P=0.004)、预后危险度分层高危(HR=1.595,95%CI:1.060~2.856,P=0.031)、lncRNA HOXA-AS2相对表达量≥3.54(HR=1.780,95%CI:1.152~3.168,P=0.038)、miR-124-3p相对表达量<0.99(HR=0.500,95%CI:0.279~0.897,P=0.020)是AML患者预后不良的危险因素。结论白细胞计数≥30×10^(9)/L、骨髓原始细胞比率≥70%、预后危险度分层高危的AML患者lncRNA HOXA-AS2表达增高、miR-124-3p表达降低,lncRNA HOXA-AS2相对表达量≥3.54、miR-124-3p相对表达量<0.99的AML患者可能预后不良。

Objective To observe the expressions of long non-coding RNA(lncRNA)homeobox gene A-antisense strand 2(HOXA-AS2)and miR-124-3 p in plasma of patients with acute myeloid leukemia(AML),and to explore their relationships with clinicopathological features and prognosis.Methods Totally 116 patients with AML(AML group)were given standard chemotherapy according to the AML classification.Another 116 healthy volunteers during the same period were as controls(control group).The relative expressions of lncRNA HOXA-AS2 and miR-124-3 p in plasma were detected by real-time fluorescence quantitative PCR on admission in AML group and during physical examination in control group,and were compared in AML patients with different clinicopathological features.The correlation between lncRNA HOXA-AS2 and miR-124-3 p in AML patients was analyzed by Pearson correlation method.AML patients were divided into 62 patients with lncRNA HOXA-AS2≥3.54(highly-expressed lncRNA HOXA-AS2 group)and 54 patients with lncRNA HOXA-AS2<3.54(lowly-expressed lncRNA HOXA-AS2 group),as well as into 55 patients with miR-124-3 p≥0.99(highly-expressed miR-124-3 p group)and 61 patients with miR-124-3 p<0.99(lowly-expressed miR-124-3 p group).All patients were followed up for 3 years.Kaplan-Meier survival curves were used to analyze the3-year overall survival rate in highly-and lowly-expressed lncRNA HOXA-AS2 and miR-124-3 p groups.Multivariate Cox regression analysis was done to assess the influencing factors of poor prognosis of AML patients.Results The relative expression of lncRNA HOXA-AS2 was higher in AML group(3.54±0.98)than that in control group(0.82±0.25)(t=28.942,P<0.001),while the relative expression of miR-124-3 p was lower in AML group(0.99±0.37)than that in control group(3.47±1.29)(t=—19.945,P<0.001).The relative expression of lncRNA HOXA-AS2 was higher and the relative expression of miR-124-3 p was lower in patients with leukocyte count≥30×10^(9)/L(3.76±0.87,0.88±0.35)and bone marrow primitive cell ratio≥70%(3.75±0.89,0.91±0.36)than that in patients with leukocyte count<30×10^(9)/L(3.33±1.04,1.09±0.37)and bone marrow primitive cell ratio<70%(3.24±1.03,1.10±0.37)respectively(t=-3.171,P=0.002;t=-2.776,P=0.006).The relative expression of lncRNA HOXA-AS2 was higher in high-risk patients than that in intermediate-risk and low-risk patients(P<0.05),and higher in intermediate-risk patients than that in low-risk patients(P<0.05).The relative expression of miR-124-3 p was lower in high-risk patients than that in intermediate-risk and low-risk patients(P<0.05),and lower in intermediate-risk patients than that in low-risk patients(P<0.05).The relative expression of lncRNA HOXA-AS2 was negatively correlated with the relative expression of miR-124-3 p in AML patients(r=-0.684,P<0.001).The 3-year overall survival rate was lower in highly-expressed lncRNA HOXA-AS2 group(27.42%)than that in lowly-expressed lncRNA HOXA-AS2 group(62.96%)(χ^(2)=9.646,P=0.002),and was higher in highly-expressed miR-124-3 p group(58.18%)than that in lowly-expressed miR-124-3 p group(31.15%)(χ^(2)=10.318,P=0.001).Leukocyte count≥30×10^(9)/L(HR=2.249,95%CI:1.298-3.895,P=0.004),high risk of prognostic risk stratification(HR=1.595,95%CI:1.060-2.856,P=0.031),lncRNA HOXA-AS2≥3.54(HR=1.780,95%CI:1.152-3.168,P=0.038),and miR-124-3 p<0.99(HR=0.500,95%CI:0.279-0.897,P=0.020)were the risk factors of poor prognosis of AML patients.Conclusions LncRNA HOXA-AS2 expression is upregulated and miR-124-3 p expression is downregulated in AML patients with leukocyte count≥30×10^(9)/L,bone marrow primitive cell ratio≥70%and high risk of prognostic risk stratification.Those with lncRNA HOXA-AS2≥3.54 and miR-124-3 p<0.99 may have a poor prognosis.