Validation of a Novel Biomarker Panel for the Detection of Ovarian Cancer.
Validation of a Novel Biomarker Panel for the Detection of Ovarian Cancer.
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DOI：
10.1158/1055-9965.epi-15-1299
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发表时间：
2016-09
期刊：
影响因子：
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通讯作者：
Kulasingam V
中科院分区：
文献类型：
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作者：
Leung F;Bernardini MQ;Brown MD;Zheng Y;Molina R;Bast RC Jr;Davis G;Serra S;Diamandis EP;Kulasingam V
卵巢癌（OvCa）是最致命的妇科恶性肿瘤。我们发现OvCa生物标志物的整合组学方法已经将激肽释放酶6（KLK 6）和叶酸受体1（FOLR 1）鉴定为有希望的候选物，但这些标志物需要进一步验证。在三个独立的血清组群中研究了KLK 6、F0 LR 1、CA 125和HE 4，其中总共20名健康对照、150名良性对照和216名OvCa患者。通过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，所有生物标志物均显示OvCa患者血清中的升高（p<0.01）。总体而言，CA 125和HE 4显示出最强的能力（AUC分别为0.80和0.82）来识别OvCa患者，并且在95%的设定特异性下，将HE 4添加到CA 125将灵敏度从36%提高到67%。同样，HE 4和FOLR 1的组合是OvCa诊断的强预测因子，在设定特异性为95%时，显示出与基于CA 125的最佳模型（67%）相当的灵敏度（65%）。通过我们的整合组学方法鉴定的标志物与临床批准的标志物CA 125和HE 4类似地进行。此外，HE 4是OvCa的一个强有力的诊断标志物，应在临床环境中更常规地使用。我们的研究的意义是双重的：（1）我们已经证明了单独的HE 4和与CA 125组合的HE 4的优势，从而为增加其在临床中的使用提供了证据;以及（2）我们已经证明了我们的整合组学方法在鉴定具有与临床标志物相当的性能的新型血清标志物方面的临床效用。
Ovarian cancer (OvCa) is the most lethal gynecological malignancy. Our integrated -omics approach to OvCa 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 OvCa patients. The serum biomarker levels were determined by ELISA or automated immunoassay. All biomarkers demonstrated elevations in the sera of OvCa patients compared to controls (p<0.01). Overall, CA125 and HE4 displayed the strongest ability (AUC 0.80 and 0.82, respectively) to identify OvCa patients and the addition of HE4 to CA125 improved the sensitivity from 36% to 67% at a set specificity of 95%. As well, the combination of HE4 and FOLR1 was a strong predictor of OvCa 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 OvCa and should be used more routinely in a clinical setting. The implications of our study are two-fold: (1) we have demonstrated the strengths of HE4 alone and in combination with CA125, lending credence to increasing its usage in the clinic; and (2) we have demonstrated the clinical utility of our integrated –omics approach to identifying novel serum markers with comparable performance to clinical markers.