Department of epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.
Department of obstetrics and gynecology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
J Cell Biochem. 2019 Mar;120(3):3091-3100. doi: 10.1002/jcb.27497. Epub 2018 Nov 28.
BACKGROUND: Ovarian cancer (OC) is a major malignancy affecting a large population over the world, and a biomarker that holds diagnostic potential is of critical importance. Recently, autoantibodies have been indicated as biomarkers in multiple cancer research. The current study was designed to explore the practice of using autoantibodies in diagnostic settings by the enzyme-linked immunosorbent assay of sera with a panel of tumor-associated antigens (TAAs). METHODS: A panel of 12 TAAs was selected to detect the corresponding autoantibodies in sera sampled from 132 OC patients as case group and 147 normal healthy individuals as the control group. The diagnostic potential of this panel was evaluated by conventional evaluation, receiver operating characteristic (ROC) curve analyses, and classification tree analysis. RESULTS: When the cutoff values were set as mean ± 2 SD for normal healthy individuals, the positive rates of antibodies to any single TAA were less than 20% both in OC and in normal healthy individuals. In a parallel screening approach, a panel of nine TAAs (p53, C-myc, p90, p62, AHSG, 14-3-3zeta, RalA, Koc, and p16), obtained optimal diagnostic performance in OC with the sensitivity of 61.4% at the 85.0% specificity. In addition, when the nine TAAs were combined with CA125, the sensitivity and specificity were improved to 94.7% and 78.2%, respectively. The ROC curve analyses showed that only the area under the receiver operating characteristic curves (AUCs) of antibodies against C-myc, Koc, and RalA was beyond 0.6, which were 0.732, 0.668, and 0.665, respectively. The AUC of the combination was up to 0.914 (P < 0.05). Decision tree analysis showed that C-myc, HCC1.3, RalA, and CA125 held high potential in the detection of OC. The panel of nine TAAs also identified 78.8% of OC patients who had normal CA125 levels in their serum samples, indicating that elevated CA125 and anti-TAA antibodies appeared to be independent but supplementary biomarkers for diagnosing OC. CONCLUSIONS: In summary, the current study further supports that a customized TAA panel can serve as a promising and powerful tool for immunodiagnosis of OC and may be particularly useful in patients with normal CA125 levels.
背景：卵巢癌（OC）是一种严重影响全球大量人群的恶性肿瘤，具有诊断潜力的生物标志物至关重要。最近，自身抗体已被证明是多种癌症研究中的生物标志物。本研究旨在通过酶联免疫吸附试验（ELISA）检测血清中肿瘤相关抗原（TAA）的面板，探讨使用自身抗体进行诊断的实际应用。
方法：选择一组 12 个 TAA 来检测来自 132 名 OC 患者（病例组）和 147 名正常健康个体（对照组）的血清中相应的自身抗体。通过常规评估、接收器操作特征（ROC）曲线分析和分类树分析来评估该面板的诊断潜力。
结果：当将正常健康个体的平均值 ± 2 个标准差作为截断值时，OC 和正常健康个体中任何单个 TAA 的抗体阳性率均低于 20%。在平行筛选方法中，一组九个 TAA（p53、C-myc、p90、p62、AHSG、14-3-3zeta、RalA、Koc 和 p16）在 OC 中获得了最佳的诊断性能，在 85.0%的特异性下具有 61.4%的敏感性。此外，当将九个 TAA 与 CA125 联合使用时，敏感性和特异性分别提高到 94.7%和 78.2%。ROC 曲线分析表明，只有针对 C-myc、Koc 和 RalA 的抗体的接收器操作特征曲线（AUC）下的面积超过 0.6，分别为 0.732、0.668 和 0.665。组合的 AUC 高达 0.914（P<0.05）。决策树分析表明，C-myc、HCC1.3、RalA 和 CA125 在 OC 的检测中具有很高的潜力。九个 TAA 的面板还确定了 78.8%的 OC 患者在其血清样本中具有正常的 CA125 水平，表明升高的 CA125 和抗 TAA 抗体似乎是独立但互补的 OC 诊断标志物。
结论：总之，本研究进一步支持定制的 TAA 面板可作为 OC 免疫诊断的有前途且强大的工具，特别是在 CA125 水平正常的患者中可能更有用。
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