Association of Preoperative Circulating Hsp70 Levels with Event-Free Survival in Thoracic Oncology

Objectives/Background: Heat shock protein 70 (Hsp70) is frequently overexpressed and released from malignant tumors and is associated with tumor aggressiveness and resistance to treatment. While elevated levels of extracellular Hsp70 (eHsp70) in the blood have been associated with unfavorable tumor characteristics, its prognostic significance in the context of long-term follow-up has not yet been sufficiently analyzed. The primary objective of this study was to investigate the prognostic association between preoperative circulating eHsp70 levels and subsequent event-free survival (EFS) in patients with NSCLC undergoing thoracic surgery. Patients with pulmonary metastases from other primary tumors were analyzed as an exploratory subgroup. Methods: The association between eHsp70 levels, clinical outcome, and event-free survival in patients with malignant thoracic diseases was investigated in a retrospective study. Results: A total of 76 patients undergoing thoracic surgery for non-small cell lung cancer (NSCLC) or pulmonary metastases from other primary tumors were included and subsequently followed for disease progression, metastasis, or death. Preoperative eHsp70 levels were significantly higher in patients who experienced an adverse clinical event than in event-free patients (median 194.3 ng/mL [IQR 19.9–493.0] vs. 27.8 ng/mL [IQR 14.3–53.4], p = 0.0064). ROC analysis showed moderate discriminatory performance in the overall cohort (AUC 0.68, 95% CI 0.55–0.81), with an AUC of 0.72 (95% CI 0.56–0.88) in patients with NSCLC and 0.59 (95% CI 0.34–0.83) in patients with pulmonary metastases. In patients with NSCLC, elevated preoperative eHsp70 levels were associated with significantly shorter event-free survival (log-rank p < 0.0001). In multivariable Cox regression analysis restricted to patients with NSCLC, eHsp70 remained independently associated with shorter event-free survival after adjustment for tumor stage, age, and sex (HR 1.33, 95% CI 1.07–1.65, p = 0.010). Conclusions: These findings suggest that circulating eHsp70 may have prognostic relevance in patients with NSCLC. However, prospective validation in larger and independent cohorts is required before its clinical utility can be established.