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

Mir Alireza Hoda,Walter Klepetko,Thomas Klikovits,Balazs Hegedus,Anita Rozsas,Walter Berger,Matyas Bendek,Szilvia Torok,Ferenc Renyi-Vamos,Elisabeth Lang,Michael Grusch,Zoltan Lohinai,Viktoria Laszlo,Balazs Dome,Judit Berta

doi:10.18632/oncotarget.7796

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.

Highlights

40 % of lung cancer patients have lung adenocarcinoma (LADC, a subtype of non-small cell lung cancers (NSCLCs)
Because there has been no detailed analysis of circulating Activin A (ActA) and FST levels - and of their potential correlation - in LADC, we investigated the expressions of the members of the ActA/FST signaling system in LADC
To test whether ActA/FST complexes interfere with the ELISA detection of ActA and/or FST alone, FST and ActA levels of plasma samples were determined after treatment either with recombinant humanActA or rhFST, respectively

Summary

Introduction

40 % of lung cancer patients have lung adenocarcinoma (LADC, a subtype of non-small cell lung cancers (NSCLCs). Because there are differences with respect to prognoses between patients with the same stage, there is an urgent need to identify clinically useful non-invasive biomarkers that provide additional prognostic information to improve therapeutic decisionmaking and prediction of prognosis in this malignancy. There are only a few blood-based biomarkers currently investigated in LADC. For instance serum cytokeratin 19 fragments (CYFRA 21-1), have been investigated recently in patients with advanced LADC [1]. The analysis of other circulating tumor-derived biomarkers like cell-free nucleic acids (such as DNA and microRNAs [13]), metabolites [14, 15] or circulating tumor cells (CTCs) [13, 16, 17] might hold potential in predicting clinical outcome. Taken together, the evidence for the prognostic significance of the above mentioned biomarkers is still rather modest [18]

Methods

Results

Conclusion