弥漫大B细胞淋巴瘤患者血浆shp1基因甲基化检测及其意义
미만대B세포림파류환자혈장shp1기인갑기화검측급기의의
Plasma DNA methylation of shp1 in patients with diffuse large B cell lymphoma
  • 万方数据
    中华医学杂志 중화의학잡지
    National Medical Journal of China
    2014年 14期 1071-1075 ,共5页

    陈小双%付蓉%王一浩%宋文静%阮二宝%瞿文%王化泉%王国锦%宋嘉%王晓明%吴玉红%邢莉民%刘鸿%李丽娟%关晶%邵宗鸿

    진소쌍%부용%왕일호%송문정%원이보%구문%왕화천%왕국금%송가%왕효명%오옥홍%형리민%류홍%리려연%관정%소종홍

    淋巴瘤,大B-细胞,弥漫性%DNA甲基化%基因,shp1 淋巴瘤,大B-細胞,瀰漫性%DNA甲基化%基因,shp1
    림파류,대B-세포,미만성%DNA갑기화%기인,shp1
    Lymphoma,large B-cell,diffuse%DNA methylation%Genes,shp1
    目的：探讨弥漫大B细胞淋巴瘤（ DLBCL ）患者血浆shp1基因甲基化状态及其临床意义。方法选取2012年1月至2013年12月天津医科大学总医院血液科收治的35例初治DLBCL患者，用甲基化特异性聚合酶链反应（ MSP）方法分别检测患者血浆、外周血白细胞（ PBL）和其中28例对应福尔马林固定石蜡包埋（ FFPE）肿瘤组织中shp1甲基化，同时以6例良性淋巴组织增生和13名健康志愿者作为对照。比较各组间3种标本中shp1基因甲基化频率，分析shp1基因甲基化状态与患者临床病理指标的相关性。结果19例对照组中均未检测到shp1基因甲基化；DLBCL患者血浆、PBL、FFPE组织中 shp1基因甲基化检出率分别为51.4％（18／35）、28.6％（10／35）、64.3％（18／28）。 shp1基因甲基化在血浆和FFPE组织中有较高的一致性（κ＝0.78，P＝0.00），在PBL和FFPE组织中一致性较低（κ＝0.36，P＝0.01）。高血清乳酸脱氢酶（LDH）的患者血浆和FFPE组织中shp1基因甲基化检出率高于LDH正常患者（13／16比5／19，11／12比7／16，P＝0.02、0.04），患者PBL中shp1基因甲基化检出率与血清LDH水平无关（ P＝0.14）。结论 DLBCL患者血浆shp1基因甲基化状态能较好地反映肿瘤组织中shp1基因甲基化状态，有望成为辅助DLBCL诊断、指导靶向治疗的相对无创的生物学指标。
    목적：탐토미만대B세포림파류（ DLBCL ）환자혈장shp1기인갑기화상태급기림상의의。방법선취2012년1월지2013년12월천진의과대학총의원혈액과수치적35례초치DLBCL환자，용갑기화특이성취합매련반응（ MSP）방법분별검측환자혈장、외주혈백세포（ PBL）화기중28례대응복이마림고정석사포매（ FFPE）종류조직중shp1갑기화，동시이6례량성림파조직증생화13명건강지원자작위대조。비교각조간3충표본중shp1기인갑기화빈솔，분석shp1기인갑기화상태여환자림상병리지표적상관성。결과19례대조조중균미검측도shp1기인갑기화；DLBCL환자혈장、PBL、FFPE조직중 shp1기인갑기화검출솔분별위51.4％（18／35）、28.6％（10／35）、64.3％（18／28）。 shp1기인갑기화재혈장화FFPE조직중유교고적일치성（κ＝0.78，P＝0.00），재PBL화FFPE조직중일치성교저（κ＝0.36，P＝0.01）。고혈청유산탈경매（LDH）적환자혈장화FFPE조직중shp1기인갑기화검출솔고우LDH정상환자（13／16비5／19，11／12비7／16，P＝0.02、0.04），환자PBL중shp1기인갑기화검출솔여혈청LDH수평무관（ P＝0.14）。결론 DLBCL환자혈장shp1기인갑기화상태능교호지반영종류조직중shp1기인갑기화상태，유망성위보조DLBCL진단、지도파향치료적상대무창적생물학지표。
    Objective To explore the methylation status of shp 1 gene in plasma DNA from patients with diffuse large B cell lymphoma ( DLBCL) and discuss its possible application in molecular diagnosis and targeted therapy of the disease.Methods Methylation-specific polymerase chain reaction ( MSP) was used to detect the methylation status of shp 1 gene in plasma and peripheral blood leukocytes ( PBLs) of 35 DLBCL patients.The formaldehyde-fixed, paraffin-embedded ( FFPE) tumor tissue samples were collected from 28 DLBCL patients , 6 patients of benign lymphoid hyperplasia and 13 healthy volunteers were selected as nonmalignant controls from January 2012 to December 2013.Methylation frequencies of shp 1 gene in different groups were compared and the associations of shp 1 methylation status with clinicopathological characteristics were analyzed.Results No methylation of shp1 was detected in any of the 19 nonmalignant controls.The methylation rate of shp1 in plasma, PBLs and FFPE tumor tissues from patients with DLBCL was 51.4%(18/35), 28.6%(10/35) and 64.3%(18/28) respectively; there was a high methylation consistency of shp1 between plasma and FFPE tumor tissues (κ=0.78, P=0.00).However, methylation consistency was lower between PBLs and FFPE tumor tissues (κ=0.36, P=0.01).Methylation of shp1 was frequently detected in plasma and FFPE tumor tissues samples from patients with a high serum level of lactate dehydrogenase (13/16 vs 5/19,11/12 vs 7/16,P=0.02, 0.04).However, no such association was detected in PBLs(P =0.14).Conclusions Methylation of shp1 in plasma DNA can represent shp1 methylation status in tumor tissue.And it may serve as a promising biomarker in aiding DLBCL diagnosis and guiding targeted therapy.
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