Plasma Heat Shock Protein 90alpha as a Biomarker for the Diagnosis of Liver Cancer: An Official, Large-scale, and Multicenter Clinical Trial

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.