弥漫性大B细胞淋巴瘤患者血清和细胞中miR-21的表达及其临床意义
미만성대B세포림파류환자혈청화세포중miR-21적표체급기림상의의
Clinical significance and expression of microRNA-21 in diffuse large B-cell lymphoma cell lines and serum of patients
  • 万方数据
    中华检验医学杂志 중화검험의학잡지
    CHINESE JOURNAL OF LABORATORY MEDICINE
    2012年 5期 431-435 ,共5页

    陈卫群%卢宏达%孔德勇%刘水逸%汤贝贝%孔庆志%卢忠心

    진위군%로굉체%공덕용%류수일%탕패패%공경지%로충심

    大B细胞,弥漫性,淋巴瘤%微小RNAs%早期诊断%肿瘤标记,生物学 大B細胞,瀰漫性,淋巴瘤%微小RNAs%早期診斷%腫瘤標記,生物學
    대B세포,미만성,림파류%미소RNAs%조기진단%종류표기,생물학
    Lymphoma,large B cell,diffuse%MicroRNAs%Early detection%Tumor markers,biological
    目的 探讨微小RNA-21(miR-21)在弥漫性大B细胞淋巴瘤(DLBCL)细胞系和患者血清中的表达及其在DLBCL早期诊断、基因分型及预后判断中的意义.方法 用实时荧光定量聚合酶链反应( FQ-PCR)从细胞水平检测9种DLBCL细胞系(OCI-Ly1、OCI-Ly3、OCI-Ly4、OCI-Ly7、OCI-Ly8、OCI-Ly10、OCI-Ly18、OCI-Ly19和HBL)中miR-21的表达,及临床确诊的62例DLBCL患者(DLBCL组)、50名健康体检者(健康对照组)血清miR-21表达水平；同时,随访62例DLBCL患者无复发生存期(RFS),应用Kaplan-Meier生存曲线分析62例DLBCL患者血清miR-21表达与预后的关系.结果 健康对照组B淋巴细胞miR-21的相对表达量为1.04±0.02,9种DLBCL细胞系miR-21 相对表达量依次为2.30±0.35、237.97±56.19、5.27±0.83、3.40±0.30、11.22±2.70、133.55±16.78、6.63±0.24、4.91±0.37、81.59±6.64,9种DLBCL细胞系的miR-21表达水平均高于健康对照组(t值分别为7.3、13.7、2 1.0、6.2、8.8、13.6、6.5、39.5、18.1,P均＜0.01)；且ABC亚型细胞系(OCI-Ly3、OCI-Ly10、HBL)显著高于GCB亚型细胞系(OCI-Ly1、OCI-Ly4、OCI-Ly7、OCI-Ly8、OCI-Ly18、OCI-Ly19；t=11.18,P＜0.01).DLBCL组血清中miR-21的表达量为21.38( 10.26 ～45.21),健康对照组为1.87(1.05 ～3.97),DLBCL组血清miR-21的表达显著高于健康对照组(U=168,P=0.000).DLBCL患者中GCB亚型miR-21的表达为18.30(7.32～33.46),ABC亚型miR-21的表达为28.68( 14.92～98.44),ABC亚型miR-21的表达高于GCB亚型(U=336,P=0.043).此外,GCB型Ⅰ+Ⅱ期患者血清miR-21表达为24.75( 16.08 ～50.38),而Ⅲ+Ⅳ期为11.96(4.10～21.05)；ABC型Ⅰ+Ⅱ期患者血清miR-21表达为47.49( 25.65～295.41),而Ⅲ+Ⅳ期为16.66(5.35～44.30),Ⅰ+Ⅱ期明显高于Ⅲ+Ⅳ期(GCB型U=62,P=0.013;ABC型U=53,P=0.014).随访DLBCL患者的RFS,miR-21高表达患者预后明显好于miR-21低表达患者(U=259,P=0.035).结论 DLBCL患者血清miR-21高表达,且与DLBCL临床分级分期、基因型和预后判断密切相关,miR-21有可能成为DLBCL早期诊断、基因分型及预后判断的新分子标志.
    목적 탐토미소RNA-21(miR-21)재미만성대B세포림파류(DLBCL)세포계화환자혈청중적표체급기재DLBCL조기진단、기인분형급예후판단중적의의.방법 용실시형광정량취합매련반응( FQ-PCR)종세포수평검측9충DLBCL세포계(OCI-Ly1、OCI-Ly3、OCI-Ly4、OCI-Ly7、OCI-Ly8、OCI-Ly10、OCI-Ly18、OCI-Ly19화HBL)중miR-21적표체,급림상학진적62례DLBCL환자(DLBCL조)、50명건강체검자(건강대조조)혈청miR-21표체수평；동시,수방62례DLBCL환자무복발생존기(RFS),응용Kaplan-Meier생존곡선분석62례DLBCL환자혈청miR-21표체여예후적관계.결과 건강대조조B림파세포miR-21적상대표체량위1.04±0.02,9충DLBCL세포계miR-21 상대표체량의차위2.30±0.35、237.97±56.19、5.27±0.83、3.40±0.30、11.22±2.70、133.55±16.78、6.63±0.24、4.91±0.37、81.59±6.64,9충DLBCL세포계적miR-21표체수평균고우건강대조조(t치분별위7.3、13.7、2 1.0、6.2、8.8、13.6、6.5、39.5、18.1,P균＜0.01)；차ABC아형세포계(OCI-Ly3、OCI-Ly10、HBL)현저고우GCB아형세포계(OCI-Ly1、OCI-Ly4、OCI-Ly7、OCI-Ly8、OCI-Ly18、OCI-Ly19；t=11.18,P＜0.01).DLBCL조혈청중miR-21적표체량위21.38( 10.26 ～45.21),건강대조조위1.87(1.05 ～3.97),DLBCL조혈청miR-21적표체현저고우건강대조조(U=168,P=0.000).DLBCL환자중GCB아형miR-21적표체위18.30(7.32～33.46),ABC아형miR-21적표체위28.68( 14.92～98.44),ABC아형miR-21적표체고우GCB아형(U=336,P=0.043).차외,GCB형Ⅰ+Ⅱ기환자혈청miR-21표체위24.75( 16.08 ～50.38),이Ⅲ+Ⅳ기위11.96(4.10～21.05)；ABC형Ⅰ+Ⅱ기환자혈청miR-21표체위47.49( 25.65～295.41),이Ⅲ+Ⅳ기위16.66(5.35～44.30),Ⅰ+Ⅱ기명현고우Ⅲ+Ⅳ기(GCB형U=62,P=0.013;ABC형U=53,P=0.014).수방DLBCL환자적RFS,miR-21고표체환자예후명현호우miR-21저표체환자(U=259,P=0.035).결론 DLBCL환자혈청miR-21고표체,차여DLBCL림상분급분기、기인형화예후판단밀절상관,miR-21유가능성위DLBCL조기진단、기인분형급예후판단적신분자표지.
    Objective To study the expression of microRNA-21 ( miR-21 )in serum of patient with diffuse large B cell lymphoma (DLBCL) and DLBCL cell lines and validate the significance of miR-21 in early diagnosis,genotyping and prognosis estimates of DLBCL.Methods miR-21 expression were detected by fluorescent quantity polymerase chain reaction (FQ-PCR)in 9 lymphoma cell lines (OCI-Ly1,OCI-Ly3,OCI-Ly4,OCI-Ly7,OCI-Ly8,OCI-Ly10,OCI-Ly18,OCI-Ly19 and HBL),the serum from DLBCL patients (n =62) and health controls (n =50 ).Kaplan-Meier survival analysis was carried out during the relapsefree survival period of DLBCL patients to explore the relationship between the prognosis and microRNA expression level.Results Real time FQ-PCR result indicated that miR-21 expression was higher in DLBCL cell lines than that in normal B cells (BC).miR-21 expression in normal B cell and 9 DLBCL cell lines separately were 1.04 ± 0.02,2.30 ± 0.35,237.97 ± 56.19,5.27 ± 0.83,3.40 ± 0.30,11.22 ± 2.70,133.55 ± 16.78,6.63 ±0.24,4.91 ±0.37 and 81.59 ±6.64.Compared with BC,the expression of miR-21 were higher in all 9 DLBCL cell lines ( t =7.3,13.7,21.0,6.2,8.8,13.6,6.5,39.5,18.1 ;P ＜ 0.01 ).miR-21 expression segregates with specific molecular subgroups of DLBCL The expression was higher in the ABC type cell lines (OCI-Ly3,OCI-Ly10,HBL) than GCB type cell lines (OCI-Ly1,OCI-Ly4,OCI-Ly7,OCI-Ly8,OCI-Ly18,OCI-Ly19;t =11.18,P ＜ 0.01 ).Consistent with the cell line models,miR-21 expression levels were higher in serum from DLBCL patients [21.38 (10.26-45.21 )] than from controls [1.87 ( 1.05-3.97 ),U =168,P =0.000],and the levels were higher in DLBCL cases with an ABC-type [28.68 ( 14.92-98.44 )] than those in GCB-type [18.30 ( 7.32-33.46 ),U =336,P =0.043].MiR-21 expression levels were different in sera from different clinical stage DLBCL patients.The miR-21 level in serum of patients with subgroup ABC and subgroup GCB in stage Ⅰ and Ⅱ were 47.49( 25.65-295.41 ) and 24.74( 16.08-50.38) respectively and in stage Ⅲ and Ⅳ were 16.66 ( 5.35-44.30 ) and 11.96 ( 4.10-21.05) respectively.The levels were higher in DLBCL cases with Ⅰ -Ⅱ stage than those with Ⅲ-Ⅳ stage (U =62,P =0.013 in GCB type; U =53,P =0.014 in ABC type).Moreover,compare with relapse-free survival in DLBCL patients,high miR-21 expression was associated with well prognosis ( U =259,P =0.035).Conclusions MiR-21 is high expression in DLBCL cell lines and DLBCL patients serum.miR-21 level in sera from DLBCL patients is associated with clinical stage,molecular subgroup and prognosis estimates.MiR-21 may serve as a new biomarker to early detection,genotyping and prognosis estimates of DLBCL.
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