Mikami Mikio, Tanabe Kazuhiro, Matsuo Koji, Miyazaki Yuko, Miyazawa Masaki, Hayashi Masaru, Asai Satoshi, Ikeda Masae, Shida Masako, Hirasawa Takeshi, Kojima Nozomi, Sho Ryuichiro, Iijima Sadayo
Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan.
Advanced Technology Center, Medical Solution Segment, LSI Medience Corporation, Tokyo 1748555, Japan.
Gynecol Oncol. 2015 Dec;139(3):520-8. doi: 10.1016/j.ygyno.2015.10.012. Epub 2015 Oct 18.
While a certain fraction of endometriomas can develop de novo epithelial ovarian cancer (EOC) such as clear cell carcinoma (OCCC), there is currently no useful biomarker available for early detection of OCCC from endometriomas. The aim of this study was to describe the diagnostic utility of a novel biomarker for EOC especially for OCCC to distinguish from endometrioma.
More than 100,000 glycan structures of serum glycoproteins obtained from 134 pretreatment all stage EOC patients (including 45 OCCCs) and 159 non-cancer control women (including 36 endometriomas) were explored for a mass spectrum approach. Diagnostic accuracy of identified biomarker was compared to the one of CA-125 by comparing area under curve (AUC) and positive/negative predictive values (PPV and NPV).
A2160, a fully-sialylated alpha-chain of complement 4-binding protein, was identified as a candidate target marker. A2160 was significantly elevated in all stages of OCCC compared to with endometriomas. Diagnostic accuracy of A2160 (cutoff 1.6U/mL) to distinguish early stage OCCC from endometrioma is significantly higher than that of CA-125 (cutoff 35IU/L): AUC for A2160 versus CA-125, 0.92 versus 0.67; PPV 95% versus 64%; and NPV 85% versus 58%. In addition, fully-sialylated glycans had a higher accuracy for diagnosing EOC as compared to partially-sialylated glycans of alpha-chain of complement 4-binding protein.
Our study suggested that A2160 may be a useful biomarker to distinguish early-stage OCCC from endometrioma. This new biomarker can be potentially applied for the monitoring of endometrioma patients, making possible the early diagnosis of OCCC.
虽然一定比例的卵巢子宫内膜异位囊肿可发展为原发性上皮性卵巢癌（EOC），如透明细胞癌（OCCC），但目前尚无有效的生物标志物可用于从卵巢子宫内膜异位囊肿中早期检测出OCCC。本研究的目的是描述一种新型EOC生物标志物，尤其是用于区分OCCC与卵巢子宫内膜异位囊肿的诊断效用。
采用质谱分析法，对134例全分期EOC患者（包括45例OCCC患者）和159例非癌症对照女性（包括36例卵巢子宫内膜异位囊肿患者）治疗前血清糖蛋白的100,000多种聚糖结构进行了研究。通过比较曲线下面积（AUC）和阳性/阴性预测值（PPV和NPV），将鉴定出的生物标志物的诊断准确性与CA-125的诊断准确性进行比较。
补体4结合蛋白的完全唾液酸化α链A2160被鉴定为候选靶标标志物。与卵巢子宫内膜异位囊肿相比，A2160在OCCC的所有阶段均显著升高。A2160（临界值1.6U/mL）区分早期OCCC与卵巢子宫内膜异位囊肿的诊断准确性显著高于CA-125（临界值35IU/L）：A2160与CA-125的AUC分别为0.92和0.67；PPV分别为95%和64%；NPV分别为85%和58%。此外，与补体4结合蛋白α链的部分唾液酸化聚糖相比，完全唾液酸化聚糖对EOC的诊断准确性更高。
我们的研究表明，A2160可能是区分早期OCCC与卵巢子宫内膜异位囊肿的有用生物标志物。这种新的生物标志物可潜在地应用于卵巢子宫内膜异位囊肿患者的监测，从而实现OCCC的早期诊断。
Zotero 插件
