应用表面增强激光解吸电离-飞行时间-质谱技术筛选淋巴瘤患者血清特异性生物标志物

 目的　应用蛋白质组学表面增强激光解吸电离-飞行时间-质谱（SELDI-TOF-MS）技术筛选淋巴瘤患者血清特异性生物标志物，发现淋巴瘤早期诊断与人群筛查的血清学特异性标志。方法　应用SELDI-TOF-MS技术检测96例淋巴瘤患者血清特异性标志物，包括非霍奇金淋巴瘤（NHL）86例，霍奇金淋巴瘤（HL）10例，以30名健康体检者作为对照。采用生物化学法测定乳酸脱氢酶（LDH），酶联免疫吸附法（ELISA）测定可溶性白细胞介素-2受体（sIL-2R）、β2-微球蛋白（β2-MG）和糖链抗原125（CA125）。结果　在质荷比（M／Z）为0.2～16.0间，NHL患者有15个蛋白质含量与健康人差异有统计学意义（P＜0.01），其中M／Z为 6880、8564、8692和13 751的蛋白质低表达对淋巴瘤的敏感度与特异度高，灵敏度和特异度分别为82.29 %和80.00 %、78.13 %和73.30 %、75.00 %和80.00 %、71.88 %和83.30 %。4个蛋白质对淋巴瘤诊断的灵敏度与特异度差异均无统计学意义（P＞0.05），4个蛋白质联合检测淋巴瘤特异度达100.00 %，与LDH的灵敏度21.74 %、CA125的灵敏度56.80 %、β2-MG的灵敏度70.50 %比较，差异均有统计学意义（P＜0.05）。结论　对M／Z为6880、8564、8692和13 751的蛋白质行质谱检测，有望作为人群筛查、诊断淋巴瘤的血清学特异性标志。

Serum specific biomarkers for detection of lymphoma using SELDI-TOF-MS

Objective To identify serum specific protein biomarkers for the early diagnosis of lymphoma patients by using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) protein chip array.Methods SELDI-TOF-MS technique and weak cation exchanger (WCX2) protein chip were used to detect the serum proteomic patterns of 96 patients with lymphoma (86 patients with non-Hodgkin lymphoma and 10 patients with Hodgkin lymphoma) and 30 normal control.The serum level of LDH were measured by biochemical methods,the serum level of β2-MG and CA125 were detected by enzyme-linked immunosorbent assay (ELISA).Results Four protein peaks pattern mass/charge ratio (M/Z) 6880,8564,8692 and 13751 were decreased in lymphoma patients,and they could be used to distinguish lymphoma from healthy people and other malignant tumors.Their sensitivity and specificity were 82.29 ％ and 80.00 ％,78.13 ％ and 73.30 ％,75.00 ％ and 80.00 ％,71.88 ％ and 83.30 ％ respectively in lymphoma patients.When it was used to early diagnosing lymphoma in stage Ⅰ or Ⅱ,the sensitivity of four protein peaks pattern (M/Z 6880,8564,8692 and 13 751) were 77.55 ％,71.43 ％,71.43 ％ and 67.35 ％respectively and the specificity of all four protein peaks pattern were 100.00 ％.Four protein peaks pattern sensitivity were higher than LDH,CA125 and β2-MG respectively.Conclusion Application of SELDI-TOF-MS can be of great potential for the early diagnosis of lymphoma patients.