Circulating Hsp70 Reflects Tumor Burden and Stage-Dependent Disease Progression Across Multiple Solid Tumor Entities

Area of Science:

• Oncology
• Biomarker Discovery
• Molecular Diagnostics

Background:

• Liquid biopsy biomarkers offer insights into tumor biology and treatment response.
• Heat shock protein 70 (Hsp70), overexpressed in aggressive tumors, is found in circulation as free protein or within extracellular vesicles (EVs).
• Circulating Hsp70 (eHsp70) shows potential as a diagnostic biomarker reflecting tumor burden and stage.

Purpose of the Study:

• To evaluate circulating eHsp70 levels as a diagnostic biomarker for solid tumors.
• To assess the correlation between eHsp70 levels and tumor stage across multiple cancer entities.
• To determine the diagnostic performance of eHsp70 in distinguishing different disease stages.

Main Methods:

• Retrospective analysis of plasma samples from 389 cancer patients and 108 healthy controls.
• Quantification of circulating eHsp70 using the Hsp70-exo ELISA, detecting both free and EV-associated Hsp70.
• Statistical analysis including Kruskal-Wallis test, ROC curve analysis, and DeLong's test to assess diagnostic accuracy and stage-dependency.

Main Results:

• Circulating eHsp70 levels were significantly higher in tumor patients compared to healthy controls (p < 0.001).
• eHsp70 levels demonstrated a progressive, stage-dependent increase from early to locally advanced and metastatic disease.
• ROC analysis showed improved diagnostic performance with increasing disease stage, particularly in metastatic cancers (e.g., breast cancer AUC 0.872, sarcoma AUC 0.861, NSCLC AUC 0.835).

Conclusions:

• Circulating eHsp70 is markedly elevated in patients with malignant solid tumors.
• eHsp70 levels consistently correlate with tumor stage across diverse cancer types.
• Circulating eHsp70 serves as a valuable biomarker for assessing disease stage, monitoring progression, and potentially evaluating treatment response.