质谱检测T细胞非霍奇金淋巴瘤患者差异蛋白质的表达及其临床价值

Differential expression proteins detected by mass spectrometry in patients with T cell non-Hondgkin＇s lymphoma and their clinical value

目的研究T细胞非霍奇金淋巴瘤（T—NHL）患者血清差异蛋白质质谱的表达及其临床价值。方法应用蛋白芯片表面加强激光解吸电离一飞行时间质谱（SELDI-TOF—MS）技术wcx-2芯片检测36例T—NHL患者和30例弥漫大B细胞淋巴瘤（DLBCL）患者血清蛋白质质谱，用生物化学法测定T—NHL患者血清乳酸脱氢酶（LDH）水平，用酶联免疫吸附法（ELISA）测定β2-微球蛋白（β2-MG）水平。分析T—NHL患者与DLBCL患者间质谱检测差异表达的蛋白质，同时分析差异蛋白质丰度与疾病分期、LDH及β2-MG水平的相关性。结果与DLBCL患者比较，在T—NHL患者血清中共检测出9个差异蛋白质，其相对分子质量分别为1142．67、1451．43、1472．49、1512．03、3194．22、3267．41、3933．86、4593．12、9182．24。这些差异蛋白质的表达水平在T—NHL不同分期间差异无统计学意义（均P〉0．05）。4593．12和9182．24蛋白质质谱在T—NHL中高表达，在这两种蛋白质阳性组中，LDH表达水平分别为（290．82±29．95）u／L、（283．94±100．94）U／L，明显高于阴性组的（169．22±55．42）u／L、（169．50±59．25）U／L（t=-3．199，P=0．004；t=-2．378，P=0．026），两组蛋白质的峰值与LDH的水平呈正相关（r=0．265，r=0．178，均P〈0．01）；在这两种蛋白质阳性组与阴性组间β2-MG表达水平差异无统计学意义（P〉0．05）。其他7种蛋白质在T—NHL患者血清中低表达，LDH、β2-MG水平在这些蛋白质质谱中差异无统计学意义（均P〉0．05）。结论相对分子质量为4593．12和9182．24的蛋白质可能是鉴别T-NHL的特异血清学标志，它们可和LDH联合用于评估患者的肿瘤负荷，为临床治疗提供一定的指导。

Objective To find differential expression proteins in patients with T cell non-Hodgkin＇s lymphoma （T-NHL） by using surface-enhanced laser desorption and ionization time-of-flight mass spectrometry （SELDI-TOF-MS） technique and study their related clinical application value and prospect. Methods Serum protein of 36 T-NHL patients and 30 DLBCL patients were detected by the SELDI-TOF-MS technique and weak cation exchange （wcx-2） chip. Lactate dehydrogenase （LDH） was detected by biochemistry method. Beta- 2-microglobulin （β2-MG） was detected by enzyme-linked immunesorbent assay （ELISA）. The significant different protein spectrometry were analyzed between DLBCL patients and T-NHL patients. The correlation analysis with protein spectrometry, disease staging, LDH and β2-MG were analyzed with Spearman. Results Nine potential candidate proteins, including the peak intensity of M/Z 1142.67, 1451.43, 1472.49, 1512.03, 3194.22, 3267.41, 3933.86, 4593.12 and 9182.24, were identified in T-NHL patients. The 9 protein markers had no contact with disease staging of T-NHL （P 〉 0.05）. The protein markers of 4593.12 and 9182.24 were high level in T-NHL patients. LDH in these two protein markers＇ positive group [（290.82±29.95） U/L, （283.94±100.94） U/L] was higher than that in negative group [（169.22±55.42） U/L, （169.50±59.25） U/L] （t = -3.199, P = 0.004; t = -2.378, P = 0.026）, and LDH was positive correlation with these two protein spectrometry （r = 0.265, r = 0.178, P 〈 0.01）. There was no statistically significant difference of β2-MG between these two protein markers＇ positive group and negative group （P 〉 0.05）. The other 7 protein markers were low level in T-NHL patients, and there was no statistically significant difference of LDH and β2-MG in these 7 protein markers （P 〉 0.05）. Conclusion The protein marker of 4593.12 and 9182.24 may be the specific serological markers to identify T-NHL. The combination of these two protein markers and LDH may assess the tumor load, and provide guiding value for clinical treatment.