| Summary: | <b>Abstrac</b><b>t</b><b>: </b>High expression of <i>SERPINA1 </i>gene encoding acute phase protein, alpha1-antitrypsin (AAT), is associated with various tumors. We sought to examine the significance of <i>SERPINA1</i> 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 <i>SERPINA1</i> expression and AAT protein levels. We also studied the impact of <i>SERPINA1</i> expression and AAT protein on H1975 and H661 cell behavior, <i>in vitro</i>. Lower <i>SERPINA1</i> expression in tumor but higher in adjacent non-tumor lung tissues (<i>n</i> = 351, <i>p</i> = 0.016) as well as higher serum levels of AAT protein (<i>n</i> = 170, <i>p</i> = 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 (<i>p</i> = 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 <i>SERPINA1 </i>expression or AAT staining in the tumor tissue. Additional experiments <i>in vitro</i> revealed that external AAT and/or overexpressed <i>SERPINA1</i> gene significantly improve cancer cell migration, colony formation and resistance to apoptosis. <i>SERPINA1</i> gene and AAT protein play an active role in the pathogenesis of lung cancer and not just reflect inflammatory reaction related to cancer development.
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