神经母细胞瘤患儿骨髓PHOX2B基因临床意义探讨

Clinical significance of PHOX2B in bone marrow of patients with neuroblastoma

目的探究神经母细胞瘤(NB)患儿骨髓中PHOX2B基因表达的临床意义。方法回顾性分析2020年10月—2022年5月我院血液肿瘤科收治的47例新诊断NB患儿的临床资料,病初检测47例NB患儿骨髓PHOX2B mRNA的表达水平。结果(1)纳入研究的47例NB患儿男26例(55%),女21例(45%);中位发病年龄23.0(0.27-144)个月;INRG临床分期L1期3例(6%)、L2期15例(32%)、M期29例(62%);危险度分组极低危3例(6%)、低危9例(19%)、中危8例(17%)、高危27例(57%);病初存在骨髓转移者(骨髓形态学阳性)20例(43%),骨髓多色流式细胞术(MFC)检测阳性23例(49%),骨髓PHOX2B mRNA表达阳性31例(66%),其中3例体征存在浣熊眼的患儿PHOX2B mRNA水平均显著增高,与内参基因ABL比值分别为58%、75%、117%。(2)PHOX2B阳性组与阴性组在各种首发临床表现方面均无差异(P均>0.05);(3)PHOX2B mRNA表达水平与初诊时的骨髓细胞形态学、MFC计数结果、初诊血NSE值、初诊血LDH值、INRG分期、MYCN基因、危险度分组均具有相关性(P均<0.05)。(4)20例PHOX2B阳性组NB患儿化疗2个疗程后骨髓PHOX2B表达水平、MFC计数结果及骨髓细胞形态学阳性率较病初均明显下降(P均<0.001)。结论骨髓PHOX2B mRNA检测对于NB具有良好的特异性,可反映NB患儿体内肿瘤负荷及判断其危险度,具有一定的临床实用价值。

Objective To investigate the clinical significance of PHOX2B mRNA expression in bone marrow of children with Neuroblastoma(NB).Methods A total of 47 newly diagnosed NB children admitted to the Department of Hematology and Oncology,Children′s Hospital Affiliated to Zhengzhou University from October 2020 to May 2022 were selected as the research objects.The clinical data of patients were collected,and the amount of PHOX2B mRNA expression in the bone marrow of 47 NB children were detected at the beginning of the disease.Results(1)A total of 47 children with NB were included in the study,including 26 males(55.3%)and 21 females(44.7%);The median age of disease onset was 23.0 months(0.27-144 months);The clinical stages of International Neuroblastoma Risk Group(INRG)were 3 cases in stage L1(6.4%),15 cases in stage L2(31.9%),and 29 cases in stage M(61.7%).The risk groups were 3 cases(6.4%)in very low-risk group,9 cases(19.1%)in low-risk group,8 cases(17.0%)in medium-risk group and 27 cases(57.4%)in high-risk group.There were 20 cases(42.6%)with bone marrow metastasis(positive bone marrow cell morphology),23 cases(48.9%)with positive bone marrow MFC and 31 cases(66.0%)with positive expression of bone marrow PHOX2B mRNA at the beginning of the disease.The amount of PHOX2B mRNA expression in 3 children with raccoon eyes was significantly increased,and the ratios of PHOX2B mRNA to the reference gene ABL were 58.4%,74.6%and 116.6%,respectively.(2)There were no significant differences in various initial clinical manifestations between PHOX2B positive group and negative group(all P>0.05).(3)The amount of PHOX2B mRNA expression was correlated with bone marrow cell morphology at first diagnosis,MFC results,neuron specific enolase(NSE)levels at first diagnosis,lactate dehydrogenase(LDH)levels at first diagnosis,INRG stage,MYCN gene and risk group(P<0.05).(4)The amount of PHOX2B mRNAexpression,the results of MFC count and positive rate of bone marrow cell morphology of 20 cases in PHOX2B positive group were significantly decreased compared with the beginning of the disease(P<0.001).Conclusions The detection of PHOX2B mRNA in bone marrow has good specificity for NB,which can reflect the tumor load and estimate the risk of NB in children,it has certain clinical practical value.