抑癌基因SOCS1、SOCS3的甲基化与急性髓系白血病患者治疗转归及预后的关联分析

doi:10.6040/j.issn.1671-7554.0.2020.1734

摘要/Abstract

摘要： 目的探讨抑癌基因细胞因子信号转导抑制因子1和3(SOCS1、SOCS3)的甲基化与急性髓系白血病(AML)患者临床治疗效果及预后的关系。方法采用RT-qPCR、甲基化特异性PCR和蛋白质印迹法检测80例初治AML患者及20例正常对照者SOCS1、SOCS3基因的甲基化状态及表达水平,利用R+G显带法检测染色体核型。将AML组分别根据SOCS1、SOCS3基因是否存在甲基化分为SOCS1甲基化组(n=39)和SOCS1非甲基化组(n=41);SOCS3甲基化组(n=44)和SOCS3非甲基化组(n=36)。比较两组年龄、性别、AML分型的差异。同时比较双基因甲基化组(n=29)、单一基因甲基化组(n=25)和双非甲基化组(n=26)中融合基因、染色体核型、治疗缓解率和AML预后分层的差别。结果 AML组SOCS1、SOCS3基因甲基化率高于正常对照组(48.75% vs 0, 55% vs 0),而基因的mRNA表达AML组［SOCS1:0.080(0.003,1.090);SOCS3:0.140(0.002,1.044)］较正常对照组［SOCS1: 1.677(0.422,1.972);SOCS3:2.395±1.540］明显下降(P<0.001)。初治AML患者中, SOCS1、SOCS3甲基化组基因的 mRNA及蛋白表达水平均低于非甲基化组和正常对照组(P<0.001), AML预后不良因素WT1/ABL基因突变高于非甲基化组(χ2=9.674,P=0.008),治疗缓解率低于非甲基化组(χ2=10.583,P=0.005)。基因甲基化与预后分层的分析结果显示,SOCS1、SOCS3的甲基化状态与分子遗传学(χ2=6.137,P=0.046)预后不良相关,双非甲基化状态与细胞遗传学(χ2=6.675,P=0.036)、分子遗传学(χ2=9.693,P=0.008)预后良好相关。结论 SOCS1、SOCS3的甲基化可导致基因表达沉默,与AML的不良治疗转归及预后均有相关性。

关键词: SOCS1基因, SOCS3基因, 急性髓系白血病, 甲基化, WT1/ABL基因, FLT3-ITD基因

Abstract: Objective To explore the relationship between SOCS1 and SOCS3 methylation, remission and prognosis of acute myeloid leukemia(AML). Methods The methylation and expressions of SOCS1 and SOCS3 in 80 AML patients and 20 healthy controls were detected with RT-qPCR, MS-PCR and Western blotting. The chromosome karyotypes were determined with R+G banding method. The AML group was subdivided into SOCS1 methylation group(n=39)and SOCS1 non-methylation group(n=41), SOCS3 methylation group(n=44)and SOCS3 non-methylation group(n=36). The age, sex and AML typing were compared. The gene mutation, karyotypes, complete remission rate and AML prognosis stages were compared among the two-gene methylation group(n=29), single-gene methylation group(n=25)and double-unmethylation group(n=26). Results The AML group had higher methylation rates of SOCS1 and SOCS3 genes than the control group(48.75% vs 0, 55% vs 0), and the mRNA expressions were lower ［SOCS1: 0.080(0.003, 1.090)vs 1.677(0.422, 1.972); SOCS3: 0.140(0.002, 1.044)vs 2.395±1.540］(P<0.001). In AML patients, the mRNA and protein expressions of SOCS1 and SOCS3 methylation groups were lower than those in non-methylation groups and control group(P<0.001). The positive rate of WT1/ABL in SOCS1 and SOCS3 methylation groups was higher than that in non-methylation groups(χ2=9.674, P=0.008). The SOCS1 and SOCS3 methylation groups had a lower therapy remission rate than the non-methylation groups(χ2=10.583, P=0.005). Analysis of gene methylation and prognosis revealed that methylation of SOCS1 and SOCS3 was correlated with poor molecular abnormalities(χ2=6.137, P=0.046). Double unmethylation of SOCS1 and SOCS3 was correlated with good cytogenetics(χ2=6.675, P=0.036)and molecular abnormalities(χ2=9.693, P=0.008)of AML. Conclusion Methylation of SOCS1 and SOCS3 genes can cause gene silencing, which is associated with poor remission and prognosis of AML.

Key words: SOCS1 gene, SOCS3 gene, Acute myeloid leukemia, Methylation, WT1/ABL gene, FLT3-ITD gene

中图分类号:

R552

张晓慧,罗建民,索晓慧,孙国锋,李静. 抑癌基因SOCS1、SOCS3的甲基化与急性髓系白血病患者治疗转归及预后的关联分析[J]. 山东大学学报 (医学版), 2021, 59(3): 67-73.

ZHANG Xiaohui, LUO Jianmin, SUO Xiaohui, SUN Guofeng, LI Jing. Relationship between methylation of tumor suppressor genes SOCS1 and SOCS3 and remission and prognosis of 80 acute myeloid leukemia patients[J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 67-73.

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