Identification of α1-antitrypsin as a potential prognostic biomarker for advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors by proteomic analysis

Abstract

Objective This retrospective study attempted to identify serum biomarkers that could help to indicate treatment response in advanced nonsmall-cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment. Methods Two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used to identify proteins expressed in serum samples from NSCLC patients with long (>6-month) progression-free survival (PFS) periods, following EGFR-TKI treatment. Results Serum amyloid P component (APCS), α1-antitrypsin (AAT), fibrinogen-α (FGA), keratin type I cytoskeletal 10 (KRT10) and serotransferrin (TF) expression differed between samples taken from 18 patients before treatment (baseline) and when progressive disease (PD) was observed, during treatment. Changes in AAT, KRT10 and APCS levels were validated by Western blot analysis in the sample pool; findings were further validated by Western blot analysis in a random sample of four patients. These proteins were also present in serum samples obtained from the same patients at the partial response (PR) timepoint during EGFR-TKI treatment. AAT was upregulated at PD compared with baseline, but downregulated during the PR phase. Conclusion These observations suggest that AAT could be used as a serological biomarker for predicting the utility of EGFR-TKI treatment for advanced NSCLC.