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急性髓系白血病患者骨髓单个核细胞circRNA-KRAS表达及意义

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目的 观察急性髓系白血病(AML)患者骨髓单个核细胞中circRNA-KRAS表达变化,探讨其与AML患者临床病理特征及预后的关系.方法 2014年1月-2016年1月江苏大学附属人民医院诊治AML患者128例为AML组,同期行骨髓检查的非血液病患者30例为对照组,采用实时荧光定量PCR法检测2组骨髓单个核细胞circRNA-KRAS相对表达量;采用Spearman相关法分析AML患者circRNA-KRAS表达与血小板计数的相关性;绘制ROC曲线,评估circRNA-KRAS诊断AML的效能.AML患者均给予标准方案化疗,并根据circRNA-KRAS诊断AML的最佳截断值分为高表达组和低表达组,比较2组性别、年龄、白细胞计数、血红蛋白、血小板计数、骨髓原始细胞比例、FAB分型、染色体分型、诱导化疗后完全缓解比率;随访至2023年5月,比较2组无病生存期、总生存期.结果 对照组circRNA-KRAS相对表达量[0.163 5(0,1.000 0)]高于 AML 组[0.008 3(0,0.846 2)](U=1.694,P=0.003).128 例 AML 患者血小板计数为 46.5× 109/L(19.0×109/L,78.5×109/L),circRNA-KRAS 表达与血小板计数呈正相关(r=0.237,P=0.029).circRNA-KRAS 相对表达量以 0.056 3 为最佳截断值,诊断 AML的AUC 为 0.846(95%CI:0.767~0.925,P=0.007),灵敏度为83.3%,特异度为77.3%.128例患者中高表达组(circRNA-KRAS相对表达量≥0.056 3)29例,低表达组(circRNA-KRAS 相对表达量<0.056 3)99 例.低表达组血小板计数[30.0×109/L(19.0× 109/L,57.0× 109/L)]低于高表达组[48.0×109/L(27.0×109/L,78.5×109/L)](U=1.054,P=0.029),性别比例、年龄、白细胞计数、血红蛋白、骨髓原始细胞比例、FAB分型、染色体分型、诱导化疗后完全缓解比率与高表达组比较差异均无统计学意义(P>0.05).中位随访42个月,高表达组失访8例,低表达组失访19例,高表达组无病生存期[22.0(5.0,57.0)个月]、总生存期[32.0(14.5,73.5)个月]与低表达组[23.0(8.0,44.0)、25.5(12.0,48.0)个月]比较差异均无统计学意义(x2=0.527,P=0.468;x2=1.421,P=0.233).结论 AML患者骨髓单个核细胞circRNA-KRAS表达下调,有助于AML的诊断.
CircRNA-KRAS in bone marrow mononuclear cells of patients with acute myeloid leukemia
Objective To observe the changes of circRNA-KRAS in bone marrow mononuclear cells of patients with acute myeloid leukemia(AML),and to explore its relationships with the clinicopathologic features and prognosis of AML patients.Methods From January 2014 to January 2016,128 AML patients(AML group)were diagnosed and treated in the Affiliated People's Hospital of Jiangsu University,and another 30 patients receiving bone marrow examination due to non-hematological diseases at the same period were included as control group.The relative expression of circRNA-KRAS in bone marrow mononuclear cells was detected by real-time fluorescence quantitative PCR in two groups.Spearman's correlation coefficient was used to analyze the correlation between circRNA-KRAS and blood platelet count.ROC curves were plotted to evaluate the efficiency of circRNA-KRAS on diagnosing AML.All AML patients were given standardized protocol chemotherapy.According to the optimal cut-off value of circRNA-KRAS on diagnosing AML,128 AML patients were divided into high expression group and low expression group,and the gender,age,white blood cell count,hemoglobin,platelet count,proportion of blasts in bone marrow,FAB classification,chromosome classification,and overall response rate after chemotherapy induction were compared between two groups.The follow up was conducted till May 2023,and the disease-free survival and overall survival were compared between high and low expression groups.Results The relative expression of circRNA-KRAS was higher in control group[0.163 5(0,1.000 0)]than that in AML group[0.008 3(0,0.846 2)(U=1.694,P=0.003).The platelet count of 128 AML patients was 46.5×109/L(19.0 × 109/L,78.5 × 109/L),and circRNA-KRAS was positively correlated with platelet count(r=0.237,P=0.029).When using the optimal cut-off value of circRNA-KRAS of 0.056 3,the AUC for diagnosing AML was 0.846(95%CI:0.767-0.925,P=0.007),the sensitivity was 83.3%,and the specificity was 77.3%.In 128 AML patients,circRNA-KRAS was ≥0.056 3 in 29 patients(high expression group)and was<0.056 3 in 99 patients(low expression group).The platelet count was lower in low expression group[30.0X 109/L(19.0× 109/L,57.0× 109/L)than that in high expression group[48.0× 109/L(27.0× 109/L,78.5× 109/L)](U=1.054,P=0.029),and there were no significant differences in the gender ratio,age,white blood cell count,hemoglobin,proportion of blasts in bone marrow,FAB classification,chromosome classification,and overall response rate after chemotherapy induction between two groups(P>0.05).The median follow-up lasted for 42 months,8 patients in high expression group and 19 in low expression group were lost.There were no significant differences in the disease-free survival time[22.0(5.0,57.0)months vs.23.0(8.0,44.0)months]and the overall survival time[32.0(14.5,73.5)months vs.25.5(12.0,48.0)months]between high and low expression groups(x2=0.527,P=0.468;x2=1.421,P=0.233).Conclusion The downregulation of circRNA-KRAS expression in bone marrow mononuclear cells of AML patients contributes to the diagnosis of AML.

acute myeloid leukemiabone marrow mononuclear cellscircRNA-KRAS

周永勍、吴德龙、赵倩、邓兆群

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江苏大学附属人民医院中心实验室镇江市精确诊断与治疗重点实验室,江苏镇江 212002

江苏大学附属人民医院血液内科,江苏镇江 212002

急性髓系白血病 骨髓单个核细胞 circRNA-KRAS

国家自然科学基金

81970156

2024

中华实用诊断与治疗杂志
中华预防医学会 河南省人民医院

中华实用诊断与治疗杂志

CSTPCD
影响因子:1.276
ISSN:1674-3474
年,卷(期):2024.38(9)
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