中国癌症杂志
中國癌癥雜誌
중국암증잡지
CHINA ONCOLOGY
2012年
12期
903-908
,共6页
王虹%金松%吴德沛%孙爱宁%仇惠英%徐杨%李渭阳%王小钦
王虹%金鬆%吳德沛%孫愛寧%仇惠英%徐楊%李渭暘%王小欽
왕홍%금송%오덕패%손애저%구혜영%서양%리위양%왕소흠
骨髓增生异常综合征%预后%甲基化%分泌型卷曲相关蛋白
骨髓增生異常綜閤徵%預後%甲基化%分泌型捲麯相關蛋白
골수증생이상종합정%예후%갑기화%분비형권곡상관단백
Myelodysplatic syndrome%Prognosis%Methylation%SFRP
背景与目的:分泌型卷曲相关蛋白(secreted frizzled-related protein,SFRP)基因甲基化与许多实体瘤及白血病相关.本研究旨在探讨SFRP基因甲基化在骨髓增生异常综合征(myelodysplatic syndrome,MDS)中的预后价值.方法:采用甲基化特异性PCR的方法检测144例原发性MDS患者骨髓标本中SFRP基因甲基化状态,评价其预后价值.结果:在MDS患者中,SFRP1、2、4、5均存在甲基化,甲基化阳性率分别为41%、89.6%、43.1%和50.7%.SFRP1和SFRP5阳性率在世界卫生组织(World Health Organization,WHO)不同的亚型中差异有统计学意义(P=0.006和P=0.002);同时随着国际预后积分系统(international prognostic scoring system,IPSS)积分的增加,SFRP1和SFRP5甲基化阳性率呈上升趋势,差异有统计学意义(P=0.038和P=0.011).生存分析提示,SFRP1、SFRP4和SFRP5甲基化阳性患者与甲基化阴性患者相比,整体生存时间(overall survival,OS)明显缩短:SFRP1、SFRP4和SFRP5甲基化阳性患者的中位生存时间分别为14.1、18.5和13.2个月,而甲基化阴性患者的中位生存时间分别为31.8、31.7和31.8个月,差异有统计学意义(P=0.001, P=0.009和P=0.015).此外,SFRP5甲基化阳性患者向白血病转化的风险显著高于SFRP5甲基化阴性患者,无白血病生存(leukemia free survival, LFS)时间缩短(P=0.018).结论:SFRP1、SFRP4和SFRP5基因异常甲基化与MDS患者的OS相关;SFRP5甲基化与MDS患者向急性白血病的转化风险相关.
揹景與目的:分泌型捲麯相關蛋白(secreted frizzled-related protein,SFRP)基因甲基化與許多實體瘤及白血病相關.本研究旨在探討SFRP基因甲基化在骨髓增生異常綜閤徵(myelodysplatic syndrome,MDS)中的預後價值.方法:採用甲基化特異性PCR的方法檢測144例原髮性MDS患者骨髓標本中SFRP基因甲基化狀態,評價其預後價值.結果:在MDS患者中,SFRP1、2、4、5均存在甲基化,甲基化暘性率分彆為41%、89.6%、43.1%和50.7%.SFRP1和SFRP5暘性率在世界衛生組織(World Health Organization,WHO)不同的亞型中差異有統計學意義(P=0.006和P=0.002);同時隨著國際預後積分繫統(international prognostic scoring system,IPSS)積分的增加,SFRP1和SFRP5甲基化暘性率呈上升趨勢,差異有統計學意義(P=0.038和P=0.011).生存分析提示,SFRP1、SFRP4和SFRP5甲基化暘性患者與甲基化陰性患者相比,整體生存時間(overall survival,OS)明顯縮短:SFRP1、SFRP4和SFRP5甲基化暘性患者的中位生存時間分彆為14.1、18.5和13.2箇月,而甲基化陰性患者的中位生存時間分彆為31.8、31.7和31.8箇月,差異有統計學意義(P=0.001, P=0.009和P=0.015).此外,SFRP5甲基化暘性患者嚮白血病轉化的風險顯著高于SFRP5甲基化陰性患者,無白血病生存(leukemia free survival, LFS)時間縮短(P=0.018).結論:SFRP1、SFRP4和SFRP5基因異常甲基化與MDS患者的OS相關;SFRP5甲基化與MDS患者嚮急性白血病的轉化風險相關.
배경여목적:분비형권곡상관단백(secreted frizzled-related protein,SFRP)기인갑기화여허다실체류급백혈병상관.본연구지재탐토SFRP기인갑기화재골수증생이상종합정(myelodysplatic syndrome,MDS)중적예후개치.방법:채용갑기화특이성PCR적방법검측144례원발성MDS환자골수표본중SFRP기인갑기화상태,평개기예후개치.결과:재MDS환자중,SFRP1、2、4、5균존재갑기화,갑기화양성솔분별위41%、89.6%、43.1%화50.7%.SFRP1화SFRP5양성솔재세계위생조직(World Health Organization,WHO)불동적아형중차이유통계학의의(P=0.006화P=0.002);동시수착국제예후적분계통(international prognostic scoring system,IPSS)적분적증가,SFRP1화SFRP5갑기화양성솔정상승추세,차이유통계학의의(P=0.038화P=0.011).생존분석제시,SFRP1、SFRP4화SFRP5갑기화양성환자여갑기화음성환자상비,정체생존시간(overall survival,OS)명현축단:SFRP1、SFRP4화SFRP5갑기화양성환자적중위생존시간분별위14.1、18.5화13.2개월,이갑기화음성환자적중위생존시간분별위31.8、31.7화31.8개월,차이유통계학의의(P=0.001, P=0.009화P=0.015).차외,SFRP5갑기화양성환자향백혈병전화적풍험현저고우SFRP5갑기화음성환자,무백혈병생존(leukemia free survival, LFS)시간축단(P=0.018).결론:SFRP1、SFRP4화SFRP5기인이상갑기화여MDS환자적OS상관;SFRP5갑기화여MDS환자향급성백혈병적전화풍험상관.
Background and purpose:Methylation status of secreted frizzled-related protein (SFRP) has been implicated in the pathogenesis of many tumors as well as in leukemia. The purpose of our study was to explore the possible relationship between the methylation status of SFRP and clinical variables, and to determine their prognostic value in patients with myelodysplatic syndrome (MDS). Methods:We employed methylation-specific PCR to examine the methylation status of SFRP in 144 adult de novo MDS patients, and to determine their prognostic value in MDS. Results:Methylation of the gene promoters was observed in all 4 SFRP genes in 144 MDS patients. The methylation frequencies were as follows: 41% for SFRP1, 89.6% for SFRP2, 43.1% for SFRP4, and 50.7% for SFRP5. For SFRP1 and SFRP5, aberrant methylation was more frequent in advanced stages of World Health Organization (WHO) subtypes (P=0.006, P=0.002); In addition, the frequency of SFRP1 and SFRP5 methylation was significantly correlated with the international prognostic score system (IPSS) risk score (P=0.038, P=0.011). Evaluation of the prognostic impact of epigenetic aberrations showed that SFRP1, SFRP4, and SFRP5 methylation had a significant impact on overall survival (OS) (P=0.001, P=0.009, P=0.015, respectively). The median survival of patients with SFRP1, SFRP4, and SFRP5 methylation were 14.1, 18.5, and 13.2 months, respectively, compared to 31.8, 31.7, and 31.8 months for patients without methylation. Patients with SFRP5 methylation had a higher risk of leukemia evolution than those without SFRP5 methylation, with shorter leukemia free survival (LFS) (P=0.018). Using the number of these 3 genes present in a patient, we could classify patients into four risk groups with significantly different prognoses (OS: P=0.002, LFS: P=0.048). Conclusion:The methylation status of SFRP1, 4, and SFRP 5 was a useful prognostic marker and predicts poor prognosis in patients with MDS: methylation status of SFRP1, SFRP4, and SFRP5 was associated with poor OS in MDS and SFRP5 methylation also predicted a high risk of leukemia evolution, with shorter LFS (P=0.018).