Abstract
No biomarker can effectively screen for early gastric cancer (EGC). Players in the A disintegrin and metalloproteinase (ADAM)-natural killer group 2 member D (NKG2D) receptor axis may have a role for that. As a proof-of-concept pilot study, the expression of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17, and major histocompatibility complex (MHC) class I chain-related sequence A (MICA), a ligand for NKG2D, in gastric cancer was investigated in silico using The Cancer Genome Atlas (TCGA) database. Subsequently, the mRNA and protein expression levels of these markers except ADAM8 were tested in blood samples from patients with EGC and healthy controls. In the TCGA data analyses, EGC tissues (n = 57) expressed significantly higher mRNA levels of ADAM8, ADAM9, ADAM10, ADAM12, and ADAM17 than normal tissues (n = 35) (p < 0.005). In human blood sample analyses, ADAM12 (p = 0.0007), ADAM17 mRNA (p < 0.0001) and ADAM10 (p < 0.001(7)) protein were significantly elevated in patients with EGC (n = 27 for mRNA and n = 25 for protein) compared to the controls (n = 30 for mRNA and n = 26 for protein). Areas under the curves calculated by receiver-operating characteristic analysis for ADAM12, ADAM17 mRNA and ADAM10 protein were 0.7568 (95% confidence interval [CI]: 0.6334 to 0.8802), 0.8062 (95% CI: 0.6889 to 0.9234; p < 0.0001), and 0.8108 (95% CI: 0.6895 to 0.9320; p = 0.0001), respectively. Thus, ADAM12, ADAM17 mRNA and ADAM10 protein levels in peripheral blood could hold potential as biomarkers for screening EGC, and further investigations are required.