APOBEC-1和NF-1在上皮性卵巢癌的作用机制及临床意义

Mechanism and clinical significance of APOBEC-1 and NF-1 in epithelial ovarian cancer

目的研究载脂蛋白B m RNA编辑酶催化多肽-1(Apolipoprotein B m RNA editing enzyme,catalytic polypeptide 1,APOBEC-1)和Ⅰ型神经纤维瘤蛋白(Neurofibromatosis type 1,NF-1)在上皮性卵巢癌中的作用机制及其临床意义。方法收集2017年6月至2019年7月在我院进行手术治疗卵巢癌患者组织,包括上皮性卵巢癌患者组织(Epithelial ovarian cancer,EOC)50例、低度潜能恶性卵巢肿瘤患者组织(Low-potential malignant ovarian tumor,LMO)15例、卵巢良性肿瘤(Benign ovarian tumor,BOT)患者组织30例及正常对照组(Normal)卵巢组织40例。免疫组化、qRT-PCR和Western blot检测患者组织和细胞中APOBEC-1/NF-1的表达;ELISA检测患者外周血中APOBEC-1和NF-1的表达;分析APOBEC-1/NF-1的表达与患者年龄、临床分期、病理分级、组织学分类、淋巴结转移之间的相关性;Trans-well实验观察沉默APOBEC-1表达A2780细胞迁移和侵袭能力的变化。结果EOC患者组织中APOBEC-1蛋白水平和mRNA水平表达显著高于其他患者组织,而NF-1蛋白水平和mRNA水平表达明显低于其他患者组织(P<0.05)。EOC患者血清APOBEC-1表达显著高于其他组,NF-1明显低于其他组(P<0.05)。EOC患者组织中APOBEC-1/NF-1的表达与患者的病理分级、淋巴结转移相关(P<0.05)。沉默A2780细胞APOBEC-1表达显著抑制其迁移和侵袭能力(P<0.05)。结论APOBEC-1可能通过降低NF-1的表达参与卵巢的发生发展。

Objective To study the mechanism and clinical significance of APOBEC-1 and NF-1 in epithelial ovarian cancer.Methods Collected tissues from patients with ovarian cancer undergoing surgery in our hospital from June 2017 to July 2019,including 50 cases of epithelial ovarian cancer tissue(EOC),15 cases of low-potential malignant ovarian tumor(LMO)tissue,30 cases of benign ovarian tumor(BOT),and 40 cases of normal control(Normal)ovarian tissue.Immunohistochemistry,qRT-PCR and Western blot were used to detect the expression of APOBEC-1/NF-1 in tissues and cells;ELISA kit was used to detect the expression of APOBEC-1 and NF-1 in peripheral blood.The correlation between the expression of APOBEC-1/NF-1 and the patient’s age,clinical stage,pathological grade,histological classification,and lymph node metastasis was analyzed.Trans-well experiments were performed to observe changes in the migration and invasion capacity of A2780 cells silenced by APOBEC-1.Results The expression of APOBEC-1 protein and mRNA in EOC tissues was significantly higher,while the expression of NF-1 protein and mRNA levels was significantly lower than those in other patient’s tissues(P<0.05).The expression of APOBEC-1 in blood was significantly higher in EOC group while NF-1 was significantly lower than in the other groups(P<0.05).The overexpression of APOBEC-1/NF-1 in EOC tissues was related to the pathological grade,lymph node metastasis,and ovarian cancer classification(P<0.05).Silencing APOBEC-1 expression in A2780 cells significantly inhibited its migration and invasion ability(P<0.05).Conlusion APOBEC-1 may participate in the development of ovarian cancers by reducing the expression of NF-1.