The National Engineering Laboratory for Anti-Tumor Protein Therapeutics, Tsinghua University, Beijing, People's Republic of China; Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing, People's Republic of China; Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.
The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
EBioMedicine. 2017 Oct;24:56-63. doi: 10.1016/j.ebiom.2017.09.007. Epub 2017 Sep 12.
More sensitive biomarker is urgently needed to reduce the mortality caused by the worldwide prevalent liver cancer. This study aims to assess whether quantitative measurement of heat shock protein 90alpha (Hsp90α) in plasma can improve the diagnosis accuracy and monitor treatment response of liver cancer patients. We analyzed the data from an official (registered at ClinicalTrial.gov: NCT02324127), large-scale (1647 enrollments), and multicenter (three independent hospitals) clinical trial, which quantitatively measured plasma Hsp90α by ELISA for patients with liver cancer, patients with at-risk liver diseases (including hepatitis, liver cirrhosis, focal nodular hyperplasia), and healthy individuals. Diagnostic performance of plasma Hsp90α was evaluated by the calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). ROC curve showed plasma Hsp90α can discriminating liver cancer with a sensitivity of 92.7% and specificity of 91.3% from non-liver cancer control. Similar results were noted in detecting early-stage liver cancer (sensitivity 91.4%, specificity 91.3%). In a parallel study compared with AFP20, plasma Hsp90α exhibited a significantly higher diagnostic performance (sensitivity 93.3% vs 61.1%) in discriminating hepatocellular carcinoma (HCC) from the control. Furthermore, plasma Hsp90α measurement maintained distinctly excellent diagnostic accuracy in distinguishing AFP-negative HCC patients (sensitivity 93.9%, specificity 91.3%) and AFP-limited liver cancer (sensitivity 96.6%, specificity 90.3%). In the efficacy monitoring study, levels of plasma Hsp90α were dramatically decreased after surgery (P=0.005), and correlated significantly with tumor size during interventional therapy (P≤0.05). These findings highlight that plasma Hsp90α as a biomarker for the diagnosis of liver cancer, and can be used to evaluate the therapeutic efficacy of liver cancer patients underwent surgery, or interventional therapy.
需要更敏感的生物标志物来降低全球普遍存在的肝癌导致的死亡率。本研究旨在评估血浆中热休克蛋白 90α（Hsp90α）的定量测量是否可以提高肝癌患者的诊断准确性并监测治疗反应。我们分析了一项官方（在 ClinicalTrial.gov 注册：NCT02324127）、大规模（1647 例入组）和多中心（三个独立的医院）临床试验的数据，该试验通过 ELISA 定量测量了肝癌、高危肝病（包括肝炎、肝硬化、局灶性结节性增生）和健康个体的血浆 Hsp90α。通过计算灵敏度、特异性和接受者操作特征曲线（ROC）下的面积（AUC）来评估血浆 Hsp90α 的诊断性能。ROC 曲线表明，血浆 Hsp90α 可以区分肝癌与非肝癌对照，其敏感性为 92.7%，特异性为 91.3%。在检测早期肝癌时也观察到类似的结果（敏感性 91.4%，特异性 91.3%）。在与 AFP20 进行的平行研究中，血浆 Hsp90α在区分肝癌与对照组方面表现出明显更高的诊断性能（敏感性 93.3% vs 61.1%）。此外，血浆 Hsp90α 测量在区分 AFP 阴性肝癌患者（敏感性 93.9%，特异性 91.3%）和 AFP 有限的肝癌患者（敏感性 96.6%，特异性 90.3%）方面也保持了出色的诊断准确性。在疗效监测研究中，手术后血浆 Hsp90α水平显著降低（P=0.005），并且与介入治疗期间的肿瘤大小显著相关（P≤0.05）。这些发现强调了血浆 Hsp90α作为肝癌诊断的生物标志物的作用，可用于评估接受手术或介入治疗的肝癌患者的治疗效果。
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