一种联合生物标志物检测 panel 对卵巢癌的早期检测显示出更高的敏感性，有助于识别最具侵袭性的 II 型肿瘤。
A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours.
作者信息
Russell Matthew R, Graham Ciaren, D'Amato Alfonsina, Gentry-Maharaj Aleksandra, Ryan Andy, Kalsi Jatinderpal K, Ainley Carol, Whetton Anthony D, Menon Usha, Jacobs Ian, Graham Robert L J
机构信息
Stoller Biomarker Discovery Centre and Pathology Node, Division of Molecular and Clinical Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road Manchester, Manchester, UK.
Centre for Biomedicine, School of Healthcare Science, Manchester Metropolitan University, Manchester, UK.
出版信息
Br J Cancer. 2017 Aug 22;117(5):666-674. doi: 10.1038/bjc.2017.199. Epub 2017 Jun 29.
BACKGROUND
There is an urgent need for biomarkers for the early detection of ovarian cancer (OC). The purpose of this study was to assess whether changes in serum levels of lecithin-cholesterol acyltransferase (LCAT), sex hormone-binding globulin (SHBG), glucose-regulated protein, 78 kDa (GRP78), calprotectin and insulin-like growth factor-binding protein 2 (IGFBP2) are observed before clinical presentation and to assess the performance of these markers alone and in combination with CA125 for early detection.
METHODS
This nested case-control study used samples from the United Kingdom Collaborative Trial of Ovarian Cancer Screening trial. The sample set consisted of 482 serum samples from 49 OC subjects and 31 controls, with serial samples spanning up to 7 years pre-diagnosis. The set was divided into the following: (I) a discovery set, which included all women with only two samples from each woman, the first at<14 months and the second at >32 months to diagnosis; and (ii) a corroboration set, which included all the serial samples from the same women spanning the 7-year period. Lecithin-cholesterol acyltransferase, SHBG, GRP78, calprotectin and IGFBP2 were measured using ELISA. The performance of the markers to detect cancers pre-diagnosis was assessed.
RESULTS
A combined threshold model IGFBP2 >78.5 ng ml : LCAT <8.831 μg ml : CA125 >35 U ml outperformed CA125 alone for the earlier detection of OC. The threshold model was able to identify the most aggressive Type II cancers. In addition, it increased the lead time by 5-6 months and identified 26% of Type I subjects and 13% of Type II subjects that were not identified by CA125 alone.
CONCLUSIONS
Combined biomarker panels (IGFBP2, LCAT and CA125) outperformed CA125 up to 3 years pre-diagnosis, identifying cancers missed by CA125, providing increased diagnostic lead times for Type I and Type II OC. The model identified more aggressive Type II cancers, with women crossing the threshold dying earlier, indicating that these markers can improve on the sensitivity of CA125 alone for the early detection of OC.
背景
迫切需要用于卵巢癌（OC）早期检测的生物标志物。本研究的目的是评估在临床表现出现之前血清卵磷脂胆固醇酰基转移酶（LCAT）、性激素结合球蛋白（SHBG）、葡萄糖调节蛋白78kDa（GRP78）、钙卫蛋白和胰岛素样生长因子结合蛋白2（IGFBP2）水平是否发生变化，并评估这些标志物单独及与CA125联合用于早期检测的性能。
方法
这项巢式病例对照研究使用了来自英国卵巢癌筛查协作试验的样本。样本集包括来自49名OC受试者和31名对照的482份血清样本，系列样本跨越诊断前长达7年的时间。该样本集分为以下两类：（I）一个发现集，包括所有女性仅有的两份样本，第一份样本在诊断前<14个月，第二份样本在诊断前>32个月；（ii）一个确证集，包括来自同一女性的跨越7年的所有系列样本。使用酶联免疫吸附测定法（ELISA）检测LCAT、SHBG、GRP78、钙卫蛋白和IGFBP2。评估这些标志物在诊断前检测癌症的性能。
结果
一种联合阈值模型IGFBP2>78.5 ng/ml：LCAT<8.831 μg/ml：CA125>35 U/ml在早期检测OC方面优于单独使用CA125。该阈值模型能够识别最具侵袭性的II型癌症。此外，它将提前期延长了5至6个月，并识别出26%的I型受试者和13%的II型受试者，这些受试者是单独使用CA125无法识别的。
结论
联合生物标志物组（IGFBP2、LCAT和CA125）在诊断前3年内的表现优于CA125，能够识别CA125漏诊的癌症，为I型和II型OC提供更长的诊断提前期。该模型识别出更具侵袭性的II型癌症，越过阈值的女性死亡更早，这表明这些标志物能够提高单独使用CA125进行OC早期检测的敏感性。
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