含WW结构域的氧化还原酶在儿童骨肉瘤中表达的临床意义

Expression and clinical significance of oxido -reductase containing WW structure domain in tissue of children with osteosarcoma

目的 检测儿童骨肉瘤组织中含WW结构域的氧化还原酶(WWOX)基因的表达水平及其与其他临床病理特征的相关性.方法 本研究采用回顾性研究方法,选择2013年1月至2017年9月在新乡市第一人民医院诊治的分期为T2N0M0的153例骨肉瘤患儿为研究对象,收集治疗前活检组织标本,免疫组织化学染色分析WWOX表达水平及WWOX表达水平与骨肉瘤患儿的性别、年龄、肿瘤原发部位、对化疗反应等临床病理特征的关系,并采用Cox风险回归模型对骨肉瘤患儿无病生存期(DFS)的危险因素进行分析.结果 153例患儿中男91例,女62例,平均年龄13.9岁.WWOX表达较高的患儿化疗敏感性较好(P=0.027).WWOX的表达与微血管密度(MVD)呈负相关(r= -0.185,P=0.022),WWOX的表达与runt相关基因2(RUNX2)及血管内皮生长因子(VEGF)的表达呈负相关(r= -0.182、-0.176,均P<0.05).儿童骨肉瘤患者DFS的危险因素包括低WWOX表达、高VEGF表达、四肢肿瘤和高MVD(均P<0.05),儿童骨肉瘤患者DFS独立危险因素包括低WWOX表达和高VEGF表达(均P<0.05).结论 WWOX在儿童骨肉瘤组织中出现表达缺失是DFS的危险因素,并与骨肉瘤患者的年龄、性别和肿瘤部位等临床病理特征相对独立,有助于预测对新辅助化疗的反应, WWOX对骨肉瘤预后的影响可能是通过抑制血管生成实现的.

Objective To explore the expression levels and the relationship between the expression of oxido-reductase containing WW structure domain(WWOX)gene and clinicopathological features in children with osteosarco-ma.Methods A total of 153 children with osteosarcoma who were diagnosed and treated in the Xinxiang First People's Hospital from January 2013 to September 2017 were selected by retrospectively method.Biopsy specimens before treat-ment were collected.The clinical stage of all patients was T2N0M0.The expression of WWOX was analyzed by using im-munohistochemistry.The relationship between WWOX expression and other clinicopathological features,such as gender, age,primary site of tumor,response to chemotherapy and so on were analyzed.Cox regression was used to screen out single and multiple risk factors of disease-free survival(DFS)of preadolescent patients with osteosarcoma.Results Among the 153 cases,there were 91 males and 62 females with an average age of 13.9 years old.The sensitivity to chemotherapy in children with high WWOX expression was better (P=0.027).The expression of WWOX in specimens of osteosarcoma in children was negatively correlated with microvessel density(MVD)(r= -0.185,P=0.022),and the WWOX expression was negatively correlated with runt related gene 2(RUNX2)and VEGF expressions (r=0.182, 0.176,all P<0.05).Children with osteosarcoma DFS risk factors included low WWOX expression,high VEGF expres-sion,limbs tumors and MVD (all P<0.05);the children with osteosarcoma DFS independent risk factors included low WWOX expression and high vascular endothelial growth factor(VEGF)expression (all P<0.05).Conclusions Ex-pression deletion of WWOX in children patients with osteosarcoma is a risk factor independent of clinicopathological fea-tures such as gender,age,primary site of tumor of DFS and it may become a useful prognostic marker in the response to neoadjuvant chemotherapy.WWOX may play a role in angiogenesis in children with osteosarcoma.