Evaluation of Alpha 1-Antitrypsin for the Early Diagnosis of Colorectal Cancer

Previous proteomic studies have identified alpha 1-antitrypsin (A1AT) as a potential serum biomarker for colorectal cancer (CRC). In this case-control study, we evaluated plasma A1AT concentration and activity as a biomarker for the early diagnosis of colorectal cancer in a group of 113 sporadic CRC patients. We also analyzed A1AT gene promoter methylation, and genotypes in this group of CRC patients. The plasma A1AT and CEA concentrations were measured using the nephelometric and ELISA methods, respectively. A1AT activity was determined by Trypsin Inhibitor Capacity assay. The genomic DNA from blood samples were subjected to Z and S genotype analysis using PCR-RFLP method and the gene promoter methylation in tumors and their adjacent normal tissues was determined by methylation specific-PCR assay. The plasma levels of A1AT and CEA in patients (median, 2.3 g/L and 5.96 ng/ml, respectively) were significantly higher than those in healthy controls (medians, 1.43 g/L and 2.57 ng/ml, respectively) (p = 0.0001). The plasma A1AT activity and concentrations were positively correlated with the tumor stage and well-discriminated between early and advanced stages. The A1AT activity in plasma was the most useful marker for CRC diagnosis (median 4.8 mmol/min/ml in cases vs 1.91 mmol/min/ml in controls, p = 0.0001). No deficient Z or S alleles of A1AT was observed in patients’ genotype and the gene promoter tends to be more methylated in normal mucosa than in tumor tissues. We conclude that plasma A1AT activity has better sensitivity and specificity than CEA measurement for the early detection of CRC. Promoter demethylation might play a role in increasing plasma A1AT levels in CRC patients.