Leung Felix, Bernardini Marcus Q, Brown Marshall D, Zheng Yingye, Molina Rafael, Bast Robert C, Davis Gerard, Serra Stefano, Diamandis Eleftherios P, Kulasingam Vathany
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.
Cancer Epidemiol Biomarkers Prev. 2016 Sep;25(9):1333-40. doi: 10.1158/1055-9965.EPI-15-1299. Epub 2016 Jul 22.
Ovarian cancer is the most lethal gynecological malignancy. Our integrated -omics approach to ovarian cancer biomarker discovery has identified kallikrein 6 (KLK6) and folate-receptor 1 (FOLR1) as promising candidates but these markers require further validation.
KLK6, FOLR1, CA125, and HE4 were investigated in three independent serum cohorts with a total of 20 healthy controls, 150 benign controls, and 216 ovarian cancer patients. The serum biomarker levels were determined by ELISA or automated immunoassay.
All biomarkers demonstrated elevations in the sera of ovarian cancer patients compared with controls (P < 0.01). Overall, CA125 and HE4 displayed the strongest ability (AUC 0.80 and 0.82, respectively) to identify ovarian cancer patients and the addition of HE4 to CA125 improved the sensitivity from 36% to 67% at a set specificity of 95%. In addition, the combination of HE4 and FOLR1 was a strong predictor of ovarian cancer diagnosis, displaying comparable sensitivity (65%) to the best-performing CA125-based models (67%) at a set specificity of 95%.
The markers identified through our integrated -omics approach performed similarly to the clinically approved markers CA125 and HE4. Furthermore, HE4 represents a powerful diagnostic marker for ovarian cancer and should be used more routinely in a clinical setting.
The implications of our study are 2-fold: (i) we have demonstrated the strengths of HE4 alone and in combination with CA125, lending credence to increasing its usage in the clinic; and (ii) we have demonstrated the clinical utility of our integrated -omics approach to identifying novel serum markers with comparable performance to clinical markers. Cancer Epidemiol Biomarkers Prev; 25(9); 1333-40. ©2016 AACR.
卵巢癌是最致命的妇科恶性肿瘤。我们采用综合组学方法发现卵巢癌生物标志物，已确定激肽释放酶6（KLK6）和叶酸受体1（FOLR1）为有潜力的候选标志物，但这些标志物需要进一步验证。
在三个独立的血清队列中对KLK6、FOLR1、CA125和HE4进行研究，共有20名健康对照者、150名良性对照者和216名卵巢癌患者。通过酶联免疫吸附测定（ELISA）或自动免疫测定法测定血清生物标志物水平。
与对照相比，所有生物标志物在卵巢癌患者血清中均升高（P < 0.01）。总体而言，CA125和HE4识别卵巢癌患者的能力最强（曲线下面积分别为0.80和0.82），在设定特异性为95%时，将HE4添加到CA125中可使敏感性从36%提高到67%。此外，HE4和FOLR1的组合是卵巢癌诊断的有力预测指标，在设定特异性为95%时，其敏感性（65%）与基于CA125的最佳模型（67%）相当。
通过我们的综合组学方法鉴定的标志物与临床认可的标志物CA125和HE4表现相似。此外，HE4是卵巢癌的一种强大诊断标志物，应在临床环境中更常规地使用。
我们研究的意义有两方面：（i）我们已证明单独使用HE4以及将其与CA125联合使用的优势，这为增加其在临床中的使用提供了依据；（ii）我们已证明我们的综合组学方法在识别与临床标志物性能相当的新型血清标志物方面的临床实用性。《癌症流行病学、生物标志物与预防》；25(9)；1333 - 40。©2016美国癌症研究协会。
