In terms of ADAM12, a family of metalloprotease-related metalloproteinases, we have demonstrated that ADAM12-mediated HB-EGF (heparin binding-epidermal growth factor-like growth factor) shedding played a critical role in GC development in a preclinical model.23,24 In addition, we also previously reported that ADAM12 was highly expressed in GC tissues and offered a diagnostic biomarker for GC in another pilot study with a small sample size (N = 70).9 The AUC of uADAM12 was 0.757 in that pilot study, similar to the present data from our large-cohort study. Here, HBEGF is linked to gastric cancer.