Oncimmune ltd, Nottingham, United Kingdom.
School of Medicine, University of Nottingham, Nottingham, United Kingdom.
PLoS One. 2020 May 6;15(5):e0232247. doi: 10.1371/journal.pone.0232247. eCollection 2020.
Hepatocellular carcinoma (HCC) continues to be a leading challenge in modern oncology. Early detection via blood-based screening tests has the potential to cause a stage-shift at diagnosis and improve clinical outcomes. Tumor associated autoantibodies (TA-AAbs) have previously shown the ability to distinguish HCC from patients with high-risk liver disease. This research aimed to further show the utility of TA-AAbs as biomarkers of HCC and assess their use in combination with Alpha-fetoprotein (AFP) for detection of HCC across multiple tumor stages.
Levels of circulating G class antibodies to 44 recombinant tumor associated antigens and circulating AFP were measured in the serum of patients with HCC, non-cancerous chronic liver disease (NCCLD) and healthy controls via enzyme-linked immunosorbent assay (ELISA). TA-AAb cut-offs were set at the highest Youden's J statistic at a specificity ≥95.00%. Panels of TA-AAbs were formed using net reclassification improvement. AFP was assessed at a cut-off of 200 ng/ml.
Sensitivities ranged from 1.01% to 12.24% at specificities of 95.96% to 100.00% for single TA-AAbs. An ELISA test measuring a panel of 10 of these TA-AAbs achieved a combined sensitivity of 36.73% at a specificity of 89.89% when distinguishing HCC from NCCLD controls. At a cut-off of 200 ng/ml, AFP achieved a sensitivity of 31.63% at a specificity of 100.00% in the same cohort. Combination of the TA-AAb panel with AFP significantly increased the sensitivity for stage one (40.00%) and two (55.00%) HCC over the TA-AAb panel or AFP alone.
A panel of TA-AAbs in combination with AFP could be clinically relevant as a replacement for measuring levels of AFP alone in surveillance and diagnosis strategies. The increased early stage sensitivity could lead to a stage shift with positive prognostic outcomes.
肝细胞癌（HCC）仍然是现代肿瘤学的主要挑战。通过基于血液的筛查测试进行早期检测有可能在诊断时引起分期转移，并改善临床结果。肿瘤相关自身抗体（TA-AAb）先前已显示出能够将 HCC 与高危肝病患者区分开来的能力。本研究旨在进一步证明 TA-AAb 作为 HCC 生物标志物的效用，并评估它们在联合使用甲胎蛋白（AFP）检测多个肿瘤分期的 HCC 中的应用。
通过酶联免疫吸附试验（ELISA）测量 HCC 患者、非癌性慢性肝病（NCCLD）患者和健康对照者血清中循环 G 类抗体对 44 种重组肿瘤相关抗原和循环 AFP 的水平。TA-AAb 截止值设定为特异性≥95.00%时最高的 Youden's J 统计值。使用净重新分类改进形成 TA-AAb 面板。将 AFP 的截止值评估为 200ng/ml。
在特异性为 95.96%至 100.00%时，单个 TA-AAb 的灵敏度范围为 1.01%至 12.24%。当将 10 种此类 TA-AAb 的 ELISA 测试用于区分 HCC 与 NCCLD 对照时，组合灵敏度为 36.73%，特异性为 89.89%。在同一队列中，AFP 的截止值为 200ng/ml 时，灵敏度为 31.63%，特异性为 100.00%。与 AFP 联合使用 TA-AAb 面板显著提高了 I 期（40.00%）和 II 期（55.00%）HCC 的灵敏度，高于 TA-AAb 面板或 AFP 单独使用。
TA-AAb 组合与 AFP 联合使用可能具有临床相关性，可替代单独测量 AFP 水平用于监测和诊断策略。早期敏感性的提高可能导致分期转移，并带来积极的预后结果。
