非霍奇金淋巴瘤患者化疗前后血清蛋白质谱动态变化及其标志蛋白的筛选  

Dynamic Changes of Serum Proteomic Spectra in Patients with Non-Hodgkin′s Lymphoma(NHL) before and after Chemotherapy and Screening of Candidate Biomarkers for NHL

作　　者：凌家瑜[1] 孙晓非[1] 张星[1] 甄子俊[1] 夏奕[1] 罗文标[1] 林慧[1] 郑磊[1] 

机构地区：[1]华南肿瘤学国家重点实验室

出　　处：《癌症》2008年第10期1065-1069,共5页Chinese Journal of Cancer

基　　金：广东省自然科学基金项目(No.05001751)~~

摘　　要：背景与目的:采用现代治疗方法治疗非霍奇金淋巴瘤(non-Hodgkin’s lymphoma,NHL)完全缓解率可达70%～80%,但仍有40%～50%患者最终会复发,而微小残留病灶是复发的根源。本研究应用SELDI蛋白芯片技术,分析初诊NHL患者与正常人群血清蛋白质谱的差异和化疗前后血清蛋白质谱的变化,寻找NHL血清小分子标记物。方法:采用表面增强激光解吸电离飞行时间质谱分析技术(surface-enhanced laser desorption/ionization time of flight mass spectrometry,SELDI-TOF-MS)分析3组血清标本:44例NHL初诊组、51例正常对照组和44例完全缓解组(NHL患者自身配对)。应用Ciphergen ProteinChip 3.1软件进行原始数据的校正和分析。结果:与正常对照组比较,有1个差异蛋白峰(M11710)在NHL初诊组高表达而在CR组降低至接近正常(P<0.05);另外有9个差异蛋白峰(M3322、M4355、M6445、M6646、M8581、M8708、M8918、M13959、M15149)在NHL初诊组血清中低表达,而在CR组升高至接近正常(P<0.05)。通过建立决策树模型,发现初诊NHL患者血清存在有5个候选标志蛋白,高表达为M11710,低表达为M8581、M15149、M6646和M8918。结论:应用SELDI-TOF-MS分析可在化疗前后筛选出NHL患者血清中的标志蛋白,有可能在微小残留病监测、早期复发预测、疗效判断等方面提供有用的信息。BACKGROUND ＆ OBJECTIVE.Although the complete response rate of non-Hodgkin＇s lymphoma （NHL） is 70%-80% using modern comprehensive treatments, its relapse rate is about 40%-50%. The minimal residual disease （MRD） may be the reason of recurrence. This study was to detect dynamic changes of serum proteomic spectra in NHL patients before and after chemotherapy, thus to screen candidate markers for NHL. METHODS= The proteomic spectra from serum of 44 NHL patients before chemotherapy, 44 NHL patients who achieved complete remission （CR） after chemotherapy, and 51 healthy individuals were analyzed by surfaceenhanced laser desorption/ ionization time of flight mass spectrometry （SELDI-TOF-MS） and Ciphergen ProteinChip 3.1 software. RESULTS= Compared with the normal group, one protein peak （Ml1710） was upregulated in untreated NHL group, while was close to the normal level in CR group （P〈0.05）; nine other protein peaks （M3322, M4355, M6445, M6646, M8581, M8708, M8918, M13959, M15149） were down-regulated in untreated NHL group, while were close to normal levels in CR group （P〈 0.05）. Five candidate biomarkers for NHL were screened using the decision tree model. CONCLUSIONS= Expressions of serum proteomic spectra are different before and after chemotherapy in NHL patients. Protein signatures of NHL may be screened using SELDI mass spectrometry combined with ProteinChip software. Those signatures may be helpful in screening MRD, detecting early recurrence and predicting the response to treatments.

关 键 词：非霍奇金淋巴瘤 表面增强激光解吸电离飞行时间质谱 蛋白标记 

分 类 号：R733.1[医药卫生—肿瘤]