比较 I 型和 II 型卵巢癌候选血清标志物。
Comparison of candidate serologic markers for type I and type II ovarian cancer.
机构信息
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
出版信息
Gynecol Oncol. 2011 Sep;122(3):560-6. doi: 10.1016/j.ygyno.2011.05.039. Epub 2011 Jun 24.
OBJECTIVE
To examine the value of individual and combinations of ovarian cancer associated blood biomarkers for the discrimination between plasma of patients with type I or II ovarian cancer and disease-free volunteers.
METHODS
Levels of 14 currently promising ovarian cancer-related biomarkers, including CA125, macrophage inhibitory factor-1 (MIF-1), leptin, prolactin, osteopontin (OPN), insulin-like growth factor-II (IGF-II), autoantibodies (AAbs) to eight proteins: p53, NY-ESO-1, p16, ALPP, CTSD, B23, GRP78, and SSX, were measured in the plasma of 151 ovarian cancer patients, 23 with borderline ovarian tumors, 55 with benign tumors and 75 healthy controls.
RESULTS
When examined individually, seven candidate biomarkers (MIF, Prolactin, CA-125, OPN, Leptin, IGF-II and p53 AAbs) had significantly different plasma levels between type II ovarian cancer patients and healthy controls. Based on the receiver operating characteristic (ROC) curves constructed and area under the curve (AUC) calculated, CA125 exhibited the greatest power to discriminate the plasma samples of type II cancer patients from normal volunteers (AUC 0.9310), followed by IGF-II (AUC 0.8514), OPN (AUC 0.7888), leptin (AUC 0.7571), prolactin (AUC 0.7247), p53 AAbs (AUC 0.7033), and MIF (AUC 0.6992). p53 AAbs levels exhibited the lowest correlation with CA125 levels among the six markers, suggesting the potential of p53 AAbs as a biomarker independent of CA125. Indeed, p53 AAbs increased the AUC of ROC curve to the greatest extent when combining CA125 with one of the other markers. At a fixed specificity of 100%, the addition of p53 AAbs to CA125 increased sensitivity from 73.8% to 85.7% to discriminate type II cancer patients from normal controls. Notably, seropositivity of p53 AAbs is comparable in type II ovarian cancer patients with negative and positive CA125, but has no value for type I ovarian cancer patients.
CONCLUSIONS
p53 AAbs might be a useful blood-based biomarker for the detection of type II ovarian cancer, especially when combined with CA125 levels.
目的
探讨卵巢癌相关血液生物标志物个体及联合检测在区分 I 型和 II 型卵巢癌患者与无病志愿者血浆中的价值。
方法
检测了 151 例卵巢癌患者、23 例交界性卵巢肿瘤患者、55 例良性肿瘤患者和 75 例健康对照者血浆中 14 种目前有前途的卵巢癌相关生物标志物，包括 CA125、巨噬细胞抑制因子-1（MIF-1）、瘦素、催乳素、骨桥蛋白（OPN）、胰岛素样生长因子-II（IGF-II）和 8 种蛋白质的自身抗体（AAbs）：p53、NY-ESO-1、p16、ALPP、CTSD、B23、GRP78 和 SSX。
结果
当单独检查时，7 种候选生物标志物（MIF、催乳素、CA-125、OPN、瘦素、IGF-II 和 p53 AAbs）在 II 型卵巢癌患者和健康对照者的血浆水平有显著差异。根据构建的受试者工作特征（ROC）曲线和计算的曲线下面积（AUC），CA125 显示出最大的区分 II 型癌症患者和正常志愿者血浆样本的能力（AUC 0.9310），其次是 IGF-II（AUC 0.8514）、OPN（AUC 0.7888）、瘦素（AUC 0.7571）、催乳素（AUC 0.7247）、p53 AAbs（AUC 0.7033）和 MIF（AUC 0.6992）。在这 6 个标志物中，p53 AAbs 水平与 CA125 水平的相关性最低，提示 p53 AAbs 作为 CA125 以外的标志物具有潜力。事实上，当 CA125 与其他标志物之一联合使用时，p53 AAbs 可最大程度地增加 ROC 曲线的 AUC。在固定特异性为 100%的情况下，将 p53 AAbs 添加到 CA125 中可将区分 II 型癌症患者和正常对照者的敏感性从 73.8%提高到 85.7%。值得注意的是，在 CA125 阴性和阳性的 II 型卵巢癌患者中，p53 AAbs 的血清阳性率相当，但对 I 型卵巢癌患者没有价值。
结论
p53 AAbs 可能是检测 II 型卵巢癌的一种有用的基于血液的生物标志物，尤其是与 CA125 水平联合检测时。
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