FGA isoform as an indicator of targeted therapy for EGFR mutated lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) gene is frequently mutated in non-small cell lung cancer (NSCLC), which can be targeted by EGFR tyrosine kinase inhibitors (TKIs). It is hard, however, to monitor the performance of EGFR-TKI therapy dynamically. Therefore, therapeutic indicators are urgently needed. Novel antibody microarray, containing 41,472 antibodies, was used for comprehensive analyzing of serum samples from 9 normal subjects and 9 EGFR mutated lung adenocarcinoma patients at three EGFR-TKI treatment time points, including before treatment (Baseline), partial response (PR) during treatment, and disease progression (PD) after resistance. Through microarray data analysis, five candidate antibodies were screened out for confirmation in serum samples and the verified one was utilized for candidate protein identification through immunoprecipitation-mass spectrometry strategy. A novel protein, isoform 2 of fibrinogen alpha chain (FGA2), was revealed and verified in the discovery sample set. Its performance as therapy indicator was further evaluated in another pre-validation sample set (n = 60). Our data confirmed that serum FGA2 level was correlated with EGFR-TKI response (p < 0.05). The expression and secretion of FGA2 in hepatocytes were inhibited by EGFR-TKI, partially explaining the downregulation of FGA2 in serum. Our results demonstrate that FGA2 is an indicator of targeted therapy for EGFR mutated lung adenocarcinoma. KEY MESSAGES: Antibody microarray was coupled with mass spectrometry for proteomics research. FGA2 was discovered as an indicator of EGFR-TKI targeted therapy. FGA2's expression/secretion in hepatocytes was dramatically inhibited by EGFR-TKI.