Heat-shock protein 90α is a potential prognostic and predictive biomarker in hepatocellular carcinoma: a large-scale and multicenter study.

Background: Although the diagnostic value of plasma heat-shock protein 90α (HSP90α) in hepatocellular carcinoma (HCC) has been previously reported, the causal effect of the plasma HSP90α levels on HCC prognosis remains largely unclear. To this extent, we sought to assess whether the plasma HSP90α acts as a prognostic factor for HCC patients.

Methods: A total of 2150 HCC patients were included in this retrospective study between August 2016 and July 2021. Plasma HSP90α levels were tested within a week before treatment and their association with prognosis was assessed.

Results: An optimal cutoff value of 143.5 for the HSP90α based on the overall survival (OS) was determined using the X-tile software. HCC patients with HSP90α < 143.5 ng/mL (low HSP90α) before and after propensity score matching (PSM) indicated longer median OS (mOS) relative to those with HSP90α ≥ 143.5 ng/mL (high HSP90α) (37.0 vs. 9.0 months, p < 0.001; 19.2 vs. 9.6 months, p < 0.001; respectively). In addition, the high HSP90α plasma level is an independent poor prognostic factor for OS in HCC patients. In our subgroup analysis, including the supportive care group, surgery group, transarterial chemoembolization (TACE) group, adjuvant TACE group, an immune checkpoint inhibitor (ICI) plus targeted therapy group, and TACE plus ICI group, the high HSP90α group demonstrated better OS compared to the low HSP90α group. Moreover, in the supportive care, TACE, ICI plus targeted therapy, TACE plus ICI groups, and high HSP90α levels were also an independent poor prognostic factors for OS.

Conclusions: Our study confirmed that the plasma HSP90α level can be used as a prognostic biomarker for HCC.