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目的定量检测神经母细胞瘤(neuroblastoma,NB)患者脑脊液(cerebrospinal fluid,CSF)中Dickkopf相关蛋白1(DKK1),探讨其作为诊断NB及疗效评估标志物的临床价值。方法实验组48例:NB患者经CT、骨髓检查确诊,年龄5个月至11岁,包括男性25例,女性23例;Evans分期:Ⅰ期5例,Ⅱ期20例,Ⅲ期15例,Ⅳ期8例。对照组50例:神经系统良性肿瘤25例,年龄5个月至65岁,包括男性13例,女性12例;化脓性脑膜炎10例,年龄5个月至6岁,包括男性4例,女性6例;脑外伤15例,年龄2～45岁,包括男性10例,女性5例。NB患者分别于治疗前、化疗结束后3 d及化疗联合手术治疗后3 d采集CSF样本各1次。ELISA法定量检测CSF中DKK1水平并做ROC曲线分析,对NB患者治疗后(化疗及化疗联合手术治疗)的CSF-DKK1水平进行随访检测。结果与对照组[(57.0±13.7)pg/mL]相比,NB患者CSF-DKK1水平显著增高[(88.7±22.9)pg/mL,P<0.01];ROC曲线分析表明,CSF-DKK1诊断NB(Cut-off=65.0 pg/mL)的灵敏度为83%,特异性为76%。与治疗前相比,化疗缓解组[n=35,(48.5±9.7)pg/mL]及化疗联合手术组[n=15,(46.4±7.8)pg/mL]的CSF-DKK1水平均显著下降(P<0.01),而化疗无效组的CSF-DKK1水平无明显变化[n=13,(89.1±25.7)pg/mL,P>0.05]。结论 NB患者脑脊液中DKK1水平显著升高且与疗效密切相关,可作为NB筛查诊断及疗效评估的标志物。
Objective To quantitatively determine the expression of Dickkopf-related protein 1 (DKK1) in cerebrospinal fluid (CSF) of patients with neuroblastoma (NB) and to evaluate its clinical value as a diagnostic marker for NB and its efficacy evaluation. Methods 48 cases of experimental group: NB patients diagnosed by CT, bone marrow examination, age 5 months to 11 years old, including 25 males and 23 females; Evans staging: Ⅰ in 5 cases, Ⅱ 20 cases, Ⅲ 15 cases, Ⅳ period in 8 cases. Control group of 50 patients: 25 cases of benign tumors of the nervous system, aged 5 months to 65 years, including 13 males and 12 females; purulent meningitis in 10 cases, aged 5 months to 6 years old, including 4 males and females 6 cases; traumatic brain injury in 15 cases, aged 2 to 45 years old, including 10 males and 5 females. NB patients were collected before treatment, chemotherapy after 3 d and 3 d after chemotherapy combined with surgical treatment of CSF samples collected 1 each. The level of DKK1 in CSF was quantitatively determined by ELISA and analyzed by ROC curve. CSF-DKK1 level in patients with NB (chemotherapy and chemotherapy combined with surgery) was followed up. Results Compared with the control group [(57.0 ± 13.7) pg / mL], the level of CSF-DKK1 was significantly increased in patients with NB [(88.7 ± 22.9) pg / mL, P <0.01]. ROC curve analysis showed that CSF- (Cut-off = 65.0 pg / mL) had a sensitivity of 83% and a specificity of 76%. The CSF-DKK1 levels in the chemotherapy-remission group (n = 35, 48.5 ± 9.7 pg / mL) and the chemotherapy-combined surgery group (n = 15, 46.4 ± 7.8 pg / mL) (P <0.01), but there was no significant change in the level of CSF-DKK1 in chemotherapy-ineffective group (n = 13, 89.1 ± 25.7 pg / mL, P> 0.05). Conclusions The level of DKK1 in cerebrospinal fluid of patients with NB was significantly increased and closely related to the curative effect, which could be used as a marker of NB screening diagnosis and efficacy evaluation.