High circulating activin A level is associated with tumor progression and predicts poor prognosis in lung adenocarcinoma

// Mir Alireza Hoda 1,2,* , Anita Rozsas 1,3,* , Elisabeth Lang 2 , Thomas Klikovits 1 , Zoltan Lohinai 3 , Szilvia Torok 3 , Judit Berta 3 , Matyas Bendek 3 , Walter Berger 2 , Balazs Hegedus 1,4 , Walter Klepetko 1 , Ferenc Renyi-Vamos 5 , Michael Grusch 2 , Balazs Dome 1,3,5,6,** and Viktoria Laszlo 1,** 1 Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria 2 Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria 3 National Koranyi Institute of Pulmonology, Budapest, Hungary 4 MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest, Hungary 5 Department of Thoracic Surgery, National Institute of Oncology and Semmelweis University, Budapest, Hungary 6 Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria * These authors share the first authorship ** These authors are co-senior authors of this study Correspondence to: Viktoria Laszlo, email: // Balazs Hegedus, email: // Keywords : activin A, lung adenocarcinoma, biomarker, metastasis, follistatin, Pathology Section Received : November 20, 2015 Accepted : February 09, 2016 Published : February 29, 2016 Abstract Activin A (ActA)/follistatin (FST) signaling has been shown to be deregulated in different tumor types including lung adenocarcinoma (LADC). Here, we report that serum ActA protein levels are significantly elevated in LADC patients (n=64) as compared to controls (n=46, p =0.015). ActA levels also correlated with more advanced disease stage ( p <0.0001) and T ( p =0.0035) and N (p=0.0002) factors. M1 patients had significantly higher ActA levels than M0 patients ( p <0.001). High serum ActA level was associated with poor overall survival ( p <0.0001) and was confirmed as an independent prognostic factor ( p =0.004). Serum FST levels were increased only in female LADC patients (vs. female controls, p=0.031). Two out of five LADC cell lines secreted biologically active ActA, while FST was produced in all of them. Transcripts of both type I and II ActA receptors were detected in all five LADC cell lines. In conclusion, our study does not only suggest that measuring blood ActA levels in LADC patients might improve the prediction of prognosis, but also indicates that this parameter might be a novel non-invasive biomarker for identifying LADC patients with organ metastases.