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CACs were decreased after surgery (median, 4 vs. 1, P  0.001) in the validation set. The CAC status between blood and tissues was highly consistent (kappa = 0.909, P  0.001). The AUC of CAC (0.823) was higher than that of CEA (0.478), SCC (0.516), NSE (0.506), ProGRP (0.519), and CYFRA21-1 (0.535) (all P  0.001). CACs might have a high value for the early diagnosis of lung cancer. These findings might need to be validated in future studies. Evidence suggested homology in genetic aberrations between the CACs and the tumor cells.