The evaluation of biological and clinical significance of alpha-1 antitrypsin in non-small cell lung cancer

Abstract

Objective: The clinical association between alpha-1 antitrypsin (AAT) blood concentration and phenotypes with non-small cell lung cancer (NSCLC) is not clear. Likewise the role of AAT in lung carcinogenesis. We investigated AAT serum levels, phenotypes and expression in NSCLC to evaluate its potential biological and clinical significance. Methods: serum and FFPE tissue samples from 206 NSCLC patients (stages I-IV) were analyzed for AAT and CRP blood concentration, AAT phenotype and AAT protein expression in tumor cells. Reference groups consisted of 183 PiMM COPD patients and 23 PiMM patients with benign lung nodules (positive chest radiograph). Results: only 10/206 (5%) NSCLC patients carried deficient AAT allele (mean AAT blood concentration 150 mg/dl). In the PiMM NSCLC patients mean AAT serum concentration (195.5 mg/dl) was significantly higher than in the PiMM COPD group (171 mg/dl) and the patients with benign lung nodules (154 mg/dl; p<0.0001). AAT concentration was significantly higher in SQC type (202 mg/dl) than ADC (175 mg/dl; p<0.029) patients, and in advanced (IIIb-IV, 247 mg/dl) versus early stage disease (I-IIIa, 190 mg/dl, p<0.0001). The AAT levels significantly correlated with CRP (R=0.6; p<0.0001), however CRP level did not differentiate NSCLC from COPD. Importantly, the strong AAT expression observed in lung tumor tissue was positively associated with the higher AAT blood levels. Conclusions: our results evidenced that local production of AAT by tumor cells significantly contribute to high levels of AAT in blood of NSCLC patients reflecting an active role of this anti-protease in lung carcinogenesis. The study is ongoing.