Cai Yuanxia,Wu Zhixiang,Wang Yi,et al.Expression of CDC5L in neuroblastoma and its clinical and prognostic significance[J].Journal of Clinical Pediatric Surgery,,18():472-479.[doi:10.3969/j.issn.1671-6353.2019.06.008]
Expression of CDC5L in neuroblastoma and its clinical and prognostic significance
- Keywords:
- Neuroblastoma; CDC5L; Pathology; Immunologic Techniques; Prognosis; Child
- CLC:
- R729;R392.7
- Abstract:
- Objective To explore the expression of CDC5L and its influence on clinicopathological characteristics in children of neuroblastoma (NB). Methods The expression of CDC5L was detected by immunohistochemistry (IHC) and Western blot (WB) in 62 NB specimens. They were divided into several groups according to gender,age,metastasis of bone marrow,tumor clinical stage (INSS),risk rating,pathological diagnosis,Shimada pathological classification and the results of lactate dehydrogenase (LDH) and neuron specific enolase (NSE). Then the difference of CDC5L expression between groups was analyzed by chi-square test. We also analyzed the overall survival rate between low and high CDC5L expression groups in 50 NB patients with complete follow-up data using Kaplan-Meier and COX regression.Results Immunohistochemical staining showed that CDC5L was predominantly located at nucleus of NB cells. Both high and low expressions of CDC5L were detected in 31/62 NB patients (50%). Both IHC and WB showed that CDC5L was more strongly expressed in NB than ganglioneuroblastoma (GNB). Both NB and GNB were derived from neural crest cells,might arise in adrenal medulla or anywhere along paraspinal sympathetic ganglia while NB was less differentiated and more malignant; We further analyzed the relationship between CDC5L expression and other clinicopathological characteristics. It was found that CDC5L expression level was higher in bone marrow infiltration group than that in non-infiltration group (χ2=5.833,P=0.016). The expression of CDC5L was higher in stage Ⅲ-Ⅳ cases than that in stage Ⅰ-Ⅱ/Ⅳ-S cases (χ2=11.328,P=0.001). Overexpression of CDC5L was usually accompanied by a frequent amplification of MYCN and amplification status of MYCN was different between high and low expression groups of CDC5L (P=0.038); CDC5L was more abundant in high-risk group than in low/intermediate-risk group (χ2=9.378,P=0.002). According to the pathological classification of Shimada,unfavorable histologic category (UFH) cases had a higher expression of CDC5L than favorable histologic category cases (χ2=7.839,P=0.005). The expression of CDC5L was higher in NSE-elevated group than that in NSE-normal group (P=0.035). Cases with LDH ≥ 587 U/L had a higher expression of CDC5L (χ2=5.547,P=0.019). Both Kaplan-Meier (P=0.002) and COX regression (HR=4.734,95%CI:1.590-14.091) showed that overexpression of CDC5L had a poor clinical prognosis. In addition,higher clinical stage (HR=7.444,95%CI:2.187-25.339),high-risk state (HR=2.749,95%CI:1.454-5.194) and pathological UFH type (HR=4.098,95%CI:1.493-11.250) were associated with worse clinical outcomes. However,when the above factors were further analyzed by COX multivariate regression,no statistical difference was observed. Conclusion A high expression of CDC5L is highly consistent with prognostic risk factors,adverse pathological types and elevated tumor markers. Kaplan-Meier curves also shows that low CDC5L group has longer survival time than high CDC5L group. Therefore CDC5L may be used as a potential molecular marker of poor prognosis,poor pathological type and elevation of tumor makers in NB children.
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Memo
收稿日期:2018-04-03。
基金项目:国家自然科学基金（编号：81572918）；国家自然科学基金（编号：81874234）；国家自然科学基金（编号：81672488）；上海市启明星计划（编号：16QA1402900）；苏州市"临床医学专家团队"引进项目（编号：SZYJTD201706）
通讯作者:吴晔明,Email:wuyeming@xinhuamed.com.cn