Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, VIC, Australia.
J Ovarian Res. 2013 Jan 22;6(1):5. doi: 10.1186/1757-2215-6-5.
Epithelial ovarian cancer is one of the leading causes of gynaecological cancer morbidity and mortality in women. Early stage ovarian cancer is usually asymptomatic, therefore, is often first diagnosed when it is widely disseminated. Currently available diagnostics lack the requisite sensitivity and specificity to be implemented as community-based screening tests. The identification of additional biomarkers may improve the diagnostic efficiency of multivariate index assays. The aims of this study were to characterise and compare the ovarian tissue immunohistochemical localisation and plasma concentrations of three putative ovarian cancer biomarkers: human cationic antimicrobial protein-18 (hCAP-18); lactoferrin; and CD163 in normal healthy women and women with ovarian cancer.
In this case-control cohort study, ovarian tissue and blood samples were obtained from 164 women (73 controls, including 28 women with benign pelvic masses; 91 cancer, including 21 women with borderline tumours). Localisation of each antigen within the ovary was assessed by immunohistochemistry and serum concentrations determined by ELISA assays.
Immunoreactive (ir) hCAP-18 and lactoferrin were identified in epithelial cells, while CD163 was predominately localised in stromal cells. Tissue ir CD163 increased significantly (P<0.05) with disease grade. Median plasma concentrations of soluble (s)CD163 were significantly greater in the cases (3220 ng/ml) than in controls (2488 ng/ml) (P< 0.01). Median plasma concentrations of hCAP-18 and lactoferrin were not significantly different between cases and controls. The classification efficiency of each biomarker (as determined by the area under the receiver operator characteristic curve; AUC) was: 0.67± 0.04; 0.62 ± 0.08 and 0.51 ± 0.07 for sCD163, hCAP-18 and lactoferrin, respectively. When the 3 biomarkers were modelled using stochastic gradient boosted logistic regression, the AUC increased to 0.95 ± 0.03.
The data obtained in this study establishes the localisation and concentrations of CD163, hCAP-18, and lactoferrin in ovarian tumours and peripheral blood. Individually, the 3 biomarkers display only modest diagnostic efficiency as assessed by AUC. When combined in a multivariate index assay, however, diagnostic efficiency increases significantly. As such, the utility of the biomarker panel, as an aid in the diagnosis of cancer in symptomatic women, is worthy of further investigation in a larger phase 2 biomarker trial.
上皮性卵巢癌是导致女性妇科癌症发病率和死亡率的主要原因之一。早期卵巢癌通常无症状，因此，通常在广泛扩散时首次诊断。目前可用的诊断方法缺乏作为社区为基础的筛查试验所必需的敏感性和特异性。鉴定其他生物标志物可能会提高多变量指数检测的诊断效率。本研究的目的是描述和比较三种潜在卵巢癌生物标志物在正常健康女性和卵巢癌患者中的卵巢组织免疫组织化学定位和血浆浓度：人阳离子抗菌蛋白 18（hCAP-18）；乳铁蛋白；和 CD163。
在这项病例对照队列研究中，从 164 名女性（73 名对照，包括 28 名患有良性盆腔肿块的女性；91 例癌症，包括 21 例患有交界性肿瘤的女性）中获得卵巢组织和血液样本。通过免疫组织化学评估每种抗原在卵巢内的定位，并通过 ELISA 测定血清浓度。
上皮细胞中鉴定出免疫反应性（ir）hCAP-18 和乳铁蛋白，而 CD163 主要定位于基质细胞。随着疾病分级的增加，组织 irCD163 显著增加（P<0.05）。可溶性（s）CD163 的中位血浆浓度在病例中显著高于对照组（3220ng/ml）（P<0.01）。病例和对照组之间 hCAP-18 和乳铁蛋白的中位血浆浓度无显著差异。每个生物标志物的分类效率（由接收器操作特征曲线下的面积确定；AUC）分别为：sCD163 为 0.67±0.04；0.62 ±0.08 和 0.51 ±0.07；hCAP-18 和乳铁蛋白。当使用随机梯度增强逻辑回归对 3 种生物标志物进行建模时，AUC 增加到 0.95 ± 0.03。
本研究获得了 CD163、hCAP-18 和乳铁蛋白在卵巢肿瘤和外周血中的定位和浓度。单独使用时，3 种生物标志物的 AUC 评估显示诊断效率仅适度。然而，当组合在多变量指数检测中时，诊断效率显著提高。因此，作为辅助有症状女性癌症诊断的生物标志物组合的效用值得在更大的 2 期生物标志物试验中进一步研究。
