Clin Chem Lab Med. 2013 Sep;51(9):1815-24. doi: 10.1515/cclm-2013-0151.
Human epididymis protein 4 (HE4), kallikrein 6 (KLK6), osteopontin (OPN) and soluble mesothelin-related peptide (SMRP) are new promising biomarkers that could integrate CA125 in epithelial ovarian cancer (EOC) diagnosis. The autoantibody response to tumor antigens is a potential tool for improving the diagnostic performances of biomarkers. The aim of this study was to assess the diagnostic potential of these biomarkers in the form of free markers and immunocomplexed with immunoglobulin M (IgM). Moreover, we analyzed the association between these markers and clinico-pathological characteristics of EOC patients.
Serum and plasma samples of 60 healthy controls, 60 ovarian benign cysts, 60 endometriosis and 60 EOCs, collected before any treatment, were tested for CICs and free antigens by immunoassays.
Immunocomplexes were characterized by poor sensitivity and specificity, since they allowed the detection only of a small number of EOC patients and were increased in patients with benign gynecological pathologies. However, the markers in the form of free antigens showed good diagnostic performances. Of note, CA125 and HE4 showed high sensitivity in the detection of the malignancy and HE4 emerged as a useful biomarker in differential diagnosis between EOC and endometriosis. Finally, elevated KLK6 and OPN, were associated with advanced FIGO stage, high grade disease, suboptimally debulked tumor and ascites.
This study confirms the diagnostic role of CA125, HE4, KLK6, OPN and SMRP, and for the first time showed that CA125, HE4, KLK6, OPN and SMRP immunocomplexed with IgM are not a potential tool for EOC diagnosis.
人附睾蛋白 4(HE4)、激肽释放酶 6(KLK6)、骨桥蛋白(OPN)和可溶性间皮素相关肽(SMRP)是新的有前途的生物标志物,可与上皮性卵巢癌(EOC)诊断中的 CA125 相结合。肿瘤抗原的自身抗体反应是提高生物标志物诊断性能的潜在工具。本研究旨在评估这些生物标志物以游离标志物和免疫复合物与免疫球蛋白 M(IgM)的形式的诊断潜力。此外,我们分析了这些标志物与 EOC 患者临床病理特征之间的关联。
收集 60 例健康对照、60 例卵巢良性囊肿、60 例子宫内膜异位症和 60 例 EOC 患者的血清和血浆样本,在任何治疗前均通过免疫测定法检测循环免疫复合物(CIC)和游离抗原。
免疫复合物的灵敏度和特异性较差,因为它们仅能检测到少数 EOC 患者,并且在良性妇科疾病患者中增加。然而,游离抗原形式的标志物表现出良好的诊断性能。值得注意的是,CA125 和 HE4 在检测恶性肿瘤方面具有较高的灵敏度,HE4 成为 EOC 和子宫内膜异位症鉴别诊断的有用生物标志物。最后,升高的 KLK6 和 OPN 与 FIGO 晚期、高级别疾病、肿瘤减灭术不理想和腹水有关。
本研究证实了 CA125、HE4、KLK6、OPN 和 SMRP 的诊断作用,并且首次表明与 IgM 免疫复合物化的 CA125、HE4、KLK6、OPN 和 SMRP 不是 EOC 诊断的潜在工具。