Abstract

Background: High mobility group box 1 protein (HMGB1) is known for its significant elevation in a multitude of tumors and benign diseases. In this study, we investigated the relevance of soluble HMGB1 for the prediction and monitoring of therapy response as well as the estimation of prognosis in advanced lung cancer. Materials and Methods: In a retrospective study, HMGB1 levels were assessed by an enzyme-linked immunosorbent assay (ELISA) in the sera of 96 patients with advanced lung cancer (79 non-small-cell lung carcinoma (NSCLC); 14 small cell lung carcinoma (SCLC), 3 Mesothelioma) prior to cycles 1, 2, and 3 of chemotherapy and correlated with radiological therapy response after 2 and 4 cycles as well as with overall survival. In addition, HMGB1 was compared with established tumor markers cytokeratin 19-fragments (CYFRA 21-1), carcinoembryonic antigen (CEA) and neuron specific enolase (NSE). Results: While pretherapeutic HMGB1 levels were not predictive or prognostically relevant in NSCLC patients, HMGB1 values prior to cycles 2 and 3 as well as kinetics from cycle 1 to 2 discriminated significantly between patients with good (remission and stable disease) and poor response (progression). Performance of HMGB1 in receiver operating characteristic (ROC) analyses of NSCLC patients, with areas under the curve (AUCs) of 0.690 at cycle 2 and 0.794 at cycle 3 as well as sensitivities of 34.4% and 37.5%, respectively, for progression at 90% specificity, was comparable with the best tumor-associated antigen CYFRA 21-1 (AUCs 0.719 and 0.799; sensitivities of 37.5% and 41.7%, respectively). Furthermore, high concentrations of HMGB1 at cycles 2 and 3 were associated with shorter overall survival in NSCLC patients. Conclusion: Soluble HMGB1 is a promising biomarker for prediction of therapy response and prognosis in advanced NSCLC patients.

Highlights

  • We evaluated the relevance of soluble High mobility group box 1 protein (HMGB1) in serum samples for the prediction and monitoring of therapy response as well as the estimation of prognosis in patients with advanced lung cancer

  • HMGB1 was higher in non-responders and differed significantly between responders and non-responders before cycles 2 and 3 as well as between cycles 1 and 2

  • HMGB1 only differed between responders and non-responders before cycle 3, with responders possessing a higher median concentration (5.02 ng/mL vs. 2.10 ng/mL)

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Summary

Introduction

We evaluated the relevance of soluble HMGB1 in serum samples for the prediction and monitoring of therapy response as well as the estimation of prognosis in patients with advanced lung cancer. For evaluation of the prognostic value of the biomarkers in NSCLC patients, Kaplan–Meier curves and Log-Rank analyses for overall survival were used.

Results
Conclusion
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