Department of Molecular and Translational Sciences, Monash University, Victoria, Australia.
Centre for Cancer Research, Hudson Institute of Medical Research, Victoria, Australia.
Cancer Epidemiol Biomarkers Prev. 2018 Feb;27(2):183-192. doi: 10.1158/1055-9965.EPI-17-0752. Epub 2017 Nov 15.
Tumor-directed circulating autoantibodies (AAb) are a well-established feature of many solid tumor types, and are often observed prior to clinical disease manifestation. As such, they may provide a good indicator of early disease development. We have conducted a pilot study to identify novel AAbs as markers of early-stage HGSOCs. A rare cohort of patients with early (FIGO stage Ia-c) HGSOCs for IgG, IgA, and IgM-mediated AAb reactivity using high-content protein arrays (containing 9,184 individual proteins). AAb reactivity against selected antigens was validated by ELISA in a second, independent cohort of individual patients. A total of 184 antigens were differentially detected in early-stage HGSOC patients compared with all other patient groups assessed. Among the six most highly detected "early-stage" antigens, anti-IgA AAbs against HSF1 and anti-IgG AAbs CCDC155 (KASH5; nesprin 5) were significantly elevated in patients with early-stage malignancy. Receiver operating characteristic (ROC) analysis suggested that AAbs against HSF1 provided better detection of early-stage malignancy than CA125 alone. Combined measurement of anti-HSF1, anti-CCDC155, and CA125 also improved efficacy at higher sensitivity. The combined measurement of anti-HSF1, anti-CCDC155, and CA125 may be useful for early-stage HGSOC detection. This is the first study to specifically identify AAbs associated with early-stage HGSOC. The presence and high frequency of specific AAbs in early-stage cancer patients warrants a larger scale examination to define their value for early disease detection at primary diagnosis and/or recurrence. .
肿瘤导向的循环自身抗体（AAb）是许多实体瘤类型的一个既定特征，通常在临床疾病表现之前就观察到。因此，它们可能是早期疾病发展的良好指标。我们进行了一项初步研究，以确定新的 AAb 作为早期卵巢高级别浆液性癌（HGSOC）的标志物。使用高内涵蛋白质阵列（包含 9184 个单个蛋白质）对早期（FIGO 分期 Ia-c）HGSOC 患者的 IgG、IgA 和 IgM 介导的 AAb 反应性进行了罕见的队列研究。在第二个独立的患者队列中，通过 ELISA 验证了针对选定抗原的 AAb 反应性。与评估的所有其他患者组相比，早期 HGSOC 患者中总共检测到 184 种不同的抗原。在六个检测到的“早期”抗原中，针对 HSF1 的抗 IgA AAb 和针对 CCDC155（KASH5；nesprin 5）的抗 IgG AAb 在早期恶性肿瘤患者中显著升高。接收者操作特征（ROC）分析表明，与单独的 CA125 相比，针对 HSF1 的 AAb 提供了更好的早期恶性肿瘤检测。同时测量抗 HSF1、抗 CCDC155 和 CA125 也提高了在更高灵敏度下的效果。同时测量抗 HSF1、抗 CCDC155 和 CA125 可能对早期 HGSOC 的检测有用。这是首次专门确定与早期 HGSOC 相关的 AAb 的研究。在早期癌症患者中存在并具有高频率的特定 AAb 表明需要进行更大规模的检查，以确定其在原发性诊断和/或复发时早期疾病检测的价值。
