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，χ2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. χ2 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 independent prognostic factors in EOC patients (all P<0.05). Similarly, the expression level of TOB1-AS1 in SKOV3 and A2780 cells were significantly higher than that in normal epithelial ovarian IOSE80 cells (all P<0.01). Cell function experiments showed that TOB1-AS1 knockdown inhibited the proliferation, migration, and invasion of SKOV3 and A2780 cells (all P<0.05). Conclusion: TOB1-AS1 is highly expressed in EOC tissues, and it is significantly related to the poor prognosis of EOC patients.TOB1-AS1 may affect the malignant progression of EOC by promoting the cell proliferation, migration, and invasion of SKOV3 and A2780 cells.

国家自然科学基金资助项目（No. 81871894）