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

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

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一2受体（sIL．2R）、B2-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13751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％、p：．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13751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。

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 13 751 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 132-MG respectively. Conclusion Application of SELDI-TOF-MS can be of great potential for the early diagnosis of lymphoma patients.