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Clinical significance of SERPINA1 gene and its encoded Alpha1-antitrypsin protein in NSCLC

Abstract: High expression of SERPINA1 gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of SERPINA1 and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lu...

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Main Authors: Ercetin, Evrim (Author) , Richtmann, Sarah (Author) , Delgado, Beatriz Martinez (Author) , Gomez-Mariano, Gema (Author) , Wrenger, Sabine (Author) , Korenbaum, Elena (Author) , Liu, Bin (Author) , DeLuca, David (Author) , Kühnel, Mark P. (Author) , Jonigk, Danny (Author) , Yuskaeva, Kadriya (Author) , Warth, Arne (Author) , Muley, Thomas (Author) , Winter, Hauke (Author) , Meister, Michael (Author) , Welte, Tobias (Author) , Janciauskiene, Sabina (Author) , Schneider, Marc (Author)
Format: Article (Journal)
Language:English
Published: 4 September 2019
In: Cancers
Year: 2019, Volume: 11, Issue: 9
ISSN:2072-6694
DOI:10.3390/cancers11091306
Online Access:Verlag, Volltext: https://doi.org/10.3390/cancers11091306
Verlag: https://www.mdpi.com/2072-6694/11/9/1306
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Author Notes:Evrim Ercetin, Sarah Richtmann, Beatriz Martinez Delgado, Gema Gomez-Mariano, Sabine Wrenger, Elena Korenbaum, Bin Liu, David DeLuca, Mark P. Kühnel, Danny Jonigk, Kadriya Yuskaeva, Arne Warth, Thomas Muley, Hauke Winter, Michael Meister, Tobias Welte, Sabina Janciauskiene and Marc A. Schneider
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Summary:Abstract: High expression of SERPINA1 gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of SERPINA1 and AAT protein in non-small-cell lung cancer (NSCLC) patients and NSCLC cell lines. Tumor and adjacent non-tumor lung tissues and serum samples from 351 NSCLC patients were analyzed for SERPINA1 expression and AAT protein levels. We also studied the impact of SERPINA1 expression and AAT protein on H1975 and H661 cell behavior, in vitro. Lower SERPINA1 expression in tumor but higher in adjacent non-tumor lung tissues (n = 351, p = 0.016) as well as higher serum levels of AAT protein (n = 170, p = 0.033) were associated with worse survival rates. Specifically, in NSCLC stage III patients, higher blood AAT levels (>2.66 mg/mL) correlated with a poor survival (p = 0.002). Intriguingly, levels of serum AAT do not correlate with levels of C-reactive protein, neutrophils-to-leukocyte ratio, and do not correlate with SERPINA1 expression or AAT staining in the tumor tissue. Additional experiments in vitro revealed that external AAT and/or overexpressed SERPINA1 gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. SERPINA1 gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.
Item Description:Gesehen am 31.10.2019
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers11091306

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