Clinical relevance of circulating activin A and follistatin in small cell lung cancer

Abstract

Circulating 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. Methods: Seventy-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. Results: Plasma 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). Conclusion: Blood 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.

The Reign of Follistatin in Tumors and Their Microenvironment: Implications for Drug Resistance

“…Under basal conditions, it is widely acknowledged that FST is typically governed by a TGF-β-Smad-induced autoregulatory negative feedback loop (Figure 6A). However, questions persist about whether this mechanism is operational in epithelial cells and why there is a frequent co-occurrence of aberrant TGF-β and FST expression in cancer [10,[139][140][141]. Figure 6.…”

Targeting activins and inhibins to treat reproductive disorders and cancer cachexia

“…Elevated activin A expression has been implicated in the pathogenesis of reproductive cancer (Menon et al 2000, Cobellis et al 2004, Tournier et al 2014, Dean et al 2017, Yi et al 2019) and various other malignancies in tissues including the breast (Di Loreto et al 1999, Mylonas et al 2005, Bashir et al 2015, Kalli et al 2019, prostate (Kang et al 2009, Nomura et al 2013, pancreas (Lonardo et al 2011, Zhong et al 2019, Mancinelli et al 2021, colon (Wildi et al 2001, Daitoku et al 2022 and lung (Seder et al 2009). Clinically, serum activin concentrations are frequently elevated in patients suffering from lung (Hoda et al 2016, Paajanen et al 2019, Barany et al 2021, breast (Reis et al 2002), colon (Loumaye et al 2015, Bauer et al 2020, Sartori et al 2021) and pancreatic cancers (Togashi et al 2015, Xu et al 2022.…”