Hu Yingchao, Zhu Yapei, Zhang Wen, Lang Jinghe, Ning Li
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People's Republic of China.
Department of Gynecologic Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China.
Onco Targets Ther. 2019 Nov 14;12:9715-9723. doi: 10.2147/OTT.S211413. eCollection 2019.
Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death in women. Due to a lacking of early detection method, its five-year survival rate is only 30%. Nevertheless, novel biomarkers for diagnosis remain to be discovered. The potential of microRNA signatures in the diagnosis of EOC has been especially described in recent years. In our previous experiments, we identified that circBNC2 was downregulated in EOC specimens, and was associated with advanced tumor stage and lymph node metastasis (LNM) by performing circRNA-sequencing analysis. The aim of this study was to explore the diagnostic value of circBNC2 in patients with epithelial ovarian cancer (EOC).
Plasma from 249 age and menopause-matched women (83 with EOC; 83 with benign ovarian cyst; 83 were healthy volunteers) was collected prior to surgery. CircBNC2 was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were analyzed using enzyme-linked immunosorbent assay (ELISA). Receiver operating curve (ROC), the area under the curve (AUC), sensitivity and specificity were estimated.
CircBNC2 was downregulated in EOC and had higher ROC AUC in comparing EOC to benign (ROC AUC 0.879, sensitivity 96.4%, specificity 80.7%) or healthy (ROC AUC 0.923, sensitivity 95.2%, specificity 85.5%) cohorts than HE4 (ROC AUC: 0.742, benign cohort; 0.779, healthy cohort) and CA125 (ROC AUC: 0.373, benign cohort; 0.713, healthy cohort). Early stage EOC vs benign (ROC AUC 0.864, sensitivity 92.0%, specificity 80.7%) and healthy (ROC AUC 0.908, sensitivity 92.0%, specificity 85.5%) cohorts could be significantly separated by circBNC2. CircBNC2 performed alike in pre- and postmenopausal women, within EOC compared to the benign or healthy cohort.
CircBNC2 is downregulated in EOC (both in tissue and plasma samples) and might present promising novel biomarker for EOC. Further studies are needed to verify our results.
CircBNC2 is downregulated in EOC and warrants investigation in a screening study in females at risk for EOC.
上皮性卵巢癌（EOC）是女性癌症死亡的第五大常见原因。由于缺乏早期检测方法，其五年生存率仅为30%。然而，仍有待发现新的诊断生物标志物。近年来，尤其描述了微小RNA特征在EOC诊断中的潜力。在我们之前的实验中，通过进行环状RNA测序分析，我们发现circBNC2在EOC标本中表达下调，并且与晚期肿瘤分期和淋巴结转移（LNM）相关。本研究的目的是探讨circBNC2在上皮性卵巢癌（EOC）患者中的诊断价值。
在手术前收集了249名年龄和绝经状态匹配的女性的血浆（83例EOC患者；83例良性卵巢囊肿患者；83名健康志愿者）。使用逆转录定量聚合酶链反应（RT-qPCR）分析circBNC2。使用酶联免疫吸附测定（ELISA）分析癌抗原125（CA125）和人附睾蛋白4（HE4）。估计受试者工作曲线（ROC）、曲线下面积（AUC）、敏感性和特异性。
circBNC2在EOC中表达下调，与HE4（良性队列的ROC AUC：0.742；健康队列的ROC AUC：0.779）和CA125（良性队列的ROC AUC：0.373；健康队列的ROC AUC：0.713）相比，在将EOC与良性（ROC AUC 0.879，敏感性96.4%，特异性80.7%）或健康（ROC AUC 0.923，敏感性95.2%，特异性85.5%）队列进行比较时，circBNC2具有更高的ROC AUC。早期EOC与良性（ROC AUC 0.864，敏感性92.0%，特异性80.7%）和健康（ROC AUC 0.908，敏感性92.0%，特异性85.5%）队列可通过circBNC2显著区分。在绝经前和绝经后女性中，以及在EOC与良性或健康队列的比较中，circBNC2的表现相似。
circBNC2在EOC（组织和血浆样本中均）表达下调，可能是EOC有前景的新型生物标志物。需要进一步研究来验证我们的结果。
circBNC2在EOC中表达下调，并值得在有EOC风险的女性筛查研究中进行调查。
