机构地区:[1]河北医科大学第四医院肿瘤免疫治疗科,河北石家庄050035 [2]河北省肿瘤研究所,河北石家庄050011 [3]河北医科大学国际合作研究干细胞实验室,河北石家庄050011
出 处:《中国肿瘤生物治疗杂志》2021年第11期1061-1067,共7页Chinese Journal of Cancer Biotherapy
基 金:国家自然科学基金资助项目(No.81871894)。
摘 要:目的:探讨ERBB2.1转导蛋白反义RNA1(transducer of ERBB2.1 antisense RNA 1,TOB1-AS1)在上皮性卵巢癌(epithelial ovarian cancer,EOC)组织中的表达情况及其临床意义,初步探讨TOB1-AS1对EOC细胞体外增殖、迁移和侵袭的影响。方法:使用TCGA数据库对EOC组织中TOB1-AS1表达情况进行分析;收集2017年7月至2018年1月在河北医科大学第四医院妇科行肿瘤切除并经病理检查证实为EOC的67例患者的肿瘤组织,收集同期因其他妇科疾病接受手术的30例患者的非肿瘤卵巢组织作为对照。采用qPCR法检测EOC组织和非肿瘤卵巢组织中TOB1-AS1的表达水平,χ^(2)检验分析TOB1-AS1的表达与不同临床病理特征之间的相关性,Kaplan-Meier和Cox比例风险回归模型分析患者生存及预后的潜在影响因素。CCK-8实验、划痕实验和Transwell实验分别检测敲低TOB1-AS1表达对EOC细胞SKOV3和A2780增殖、迁移和侵袭的影响。结果:TCGA数据库中资料和qPCR检测结果均显示,在EOC组织中TOB1-AS1的表达水平显著高于非肿瘤卵巢组织(均P<0.01)。TOB1-AS1的高表达与EOC患者较晚的FIGO分期、较差的组织分级、淋巴结转移及腹膜转移有关(均P<0.05)。Kaplan-Meier生存分析结果显示,TOB1-AS1高表达组患者术后DFS和OS均短于TOB1-AS1低表达组(均P<0.05)。Cox比例风险回归模型分析结果显示,FIGO分期、淋巴结转移、腹膜转移及TOB1-AS1表达是EOC患者预后的独立影响因素(均P<0.05)。TOB1-AS1在EOC细胞系SKOV3、A2780中的表达水平也显著高于正常卵巢上皮细胞系IOSE80(均P<0.01)。细胞功能实验结果显示,敲低TOB1-AS1可抑制SKOV3和A2780细胞的增殖、迁移和侵袭(均P<0.05)。结论:TOB1-AS1在EOC组织中高表达,与患者的不良预后显著相关。TOB1-AS1可能通过促进EOC细胞SKOV3、A2780的增殖、迁移和侵袭来影响EOC的恶性进展。Objective:To investigate the expression and clinical significance of transducer of ERBB2.1 antisense RNA1(TOB1-AS1)in epithelial ovarian cancer(EOC)tissues,and to preliminarily explore its effect on the proliferation,migration,and invasion of EOC cells in vitro.Methods:TOB1-AS1 expression in EOC tissues was analyzed using the TCGA database.The tumor tissues from 67 patients who underwent tumor resection and were pathologically confirmed as EOC in the Department of Gynecology,the Fourth Hospital of Hebei Medical University from July 2017 to January 2018 were collected for this study.In addition,30 non-tumor ovarian tissues of patients with other gynecological diseases were collected as the control in the same period.qPCR was used to detect the expression of TOB1-AS1 in EOC tissues and non-tumor ovarian tissues.χ^(2) test was used to analyze the correlation between the expression of TOB1-AS1 and different clinicopathological factors of EOC patients.Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the survival and potential influencing factors for prognosis in EOC patients.The effects of TOB1-AS1 knockdown on the proliferation,migration,and invasion of EOC SKOV3 and A2780 cells were detected by CCK-8 test,Wound-healing assay,and Transwell test,respectively.Results:TCGA database analysis and qPCR results showed the expression level of TOB1-AS1 in EOC tissues was significantly higher than that in non-tumor ovarian tissues(all P<0.01).The high expression of TOB1-AS1 was conspicuously correlated with advanced FIGO stage,poor tissue grade,lymph node metastasis,and peritoneal metastasis in patients with EOC(all P<0.05).Kaplan-Meier survival analysis showed that post-operative disease-free survival(DFS)and overall survival(OS)in the patients with high TOB1-AS1 expression were shorter than those with low TOB1-AS1 expression(all P<0.05).Cox proportional hazard regression model analysis showed that FIGO stage,lymph node metastasis,peritoneal metastasis,and TOB1-AS1 expression were indepen
关 键 词:上皮性卵巢癌 长链非编码RNA ERBB2.1转导蛋白反义RNA1 SKOV3细胞 A2780细胞 增殖 迁移 侵袭
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