Abstract

ObjectivesCirculating levels of activin A (ActA) and follistatin (FST) have been investigated in various disorders including malignancies. However, to date, their diagnostic and prognostic relevance is largely unknown in small cell lung cancer (SCLC). Our aim was to evaluate circulating ActA and FST levels as potential biomarkers in this devastating disease. MethodsSeventy-nine Caucasian SCLC patients and 67 age- and sex-matched healthy volunteers were included in this study. Circulating ActA and FST concentrations were measured by ELISA and correlated with clinicopathological parameters and long-term outcomes. ResultsPlasma ActA and FST concentrations were significantly elevated in SCLC patients when compared to healthy volunteers (p < 0.0001). Furthermore, extensive-stage SCLC patients had significantly higher circulating ActA levels than those with limited-stage disease (p = 0.0179). Circulating FST concentration was not associated with disease stage (p = 0.6859). Notably, patients with high (≥548.8 pg/ml) plasma ActA concentration exhibited significantly worse median overall survival (OS) compared to those with low (<548.8 pg/ml) ActA levels (p = 0.0009). Moreover, Cox regression analysis adjusted for clinicopathological parameters revealed that high ActA concentration is an independent predictor of shorter OS (HR: 1.932; p = 0.023). No significant differences in OS have been observed with regards to plasma FST levels (p = 0.1218). ConclusionBlood ActA levels are elevated and correlate with disease stage in SCLC patients. Measurement of circulating ActA levels might help in the estimation of prognosis in patients with SCLC.

Highlights

  • Small cell lung cancer (SCLC; accounting for approximately 13%– 15% of all lung cancers) is a highly aggressive and widely metastatic malignancy with >200,000 new patients annually worldwide [1]

  • We found that plasma activin A (ActA) concentration had a sensitivity of 73.4% and a specificity of 74.2% to distinguish SCLC patients from healthy individuals

  • With an area under the curve (AUC) of 0.815, circulating ActA could be considered as a po­ tential diagnostic biomarker for SCLC (Fig. 1b)

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Summary

Introduction

Small cell lung cancer (SCLC; accounting for approximately 13%– 15% of all lung cancers) is a highly aggressive and widely metastatic malignancy with >200,000 new patients annually worldwide [1]. In some cases patients with localized limited-stage disease can be cured with surgery (and adjuvant chemoradiotherapy), the vast majority of patients are diagnosed with extensive-stage disease when the survival rates are poor (5-year net survival is

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