Although the combined use of DKK1 and TEMs increased the AUC (0.785; 95% CI 0.709–0.861, Fig 3A) in differentiating AFP-negative HCC from LC, chronic HBV infected patients and normal controls, the combination use of DKK1 and TEMs was no better than TEMs alone in differentiating AFP-negative HCC from the other three control cohorts, and the combined use of DKK1 and TEMs did not statistically increased the AUC (0.707; 95% CI 0.577–0.837, Fig 3C) as compared with DKK1 or TEMs alone in differentiating AFP-negative HCC from LC (Fig 3C, Table 4). Here, AFP is linked to laryngotracheoesophageal cleft.