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Purpose: We aimed to evaluate the clinical significance of a disintegrin and metalloproteinase 8 (ADAM 8) as a potential bloodbiomarker for gastric cancer (GC). Materials and Methods: Blood ADAM 8 was measured by ELISA. Cytokines/chemokines [interleukin-23 (IL-23), stromal cell-derivedfactor 1α/CXC chemokine ligand 12 (SDF-1α/CXCL12), interleukin-8 (IL-8), and soluble CD40 ligand (sCD40L)] were measuredby chemiluminescent immunoassay. They were compared among five groups; normal/gastritis, high-risk, early GC (EGC),advanced GC (AGC) without distant metastasis, and AGC with distant metastasis by one-way analysis of variance in both training(n=80) and validation dataset (n=241). Clinicopathological features of GC and GC-associated cytokines were evaluated for theircorrelations with blood ADAM 8. To evaluate the diagnostic accuracy to predict GC, receiver operating characteristic (ROC) curveand logistic regression were used. Results: Blood ADAM 8 significantly increased along GC carcinogenesis in both training (ANOVA, p<0.001) and validation dataset(p<0.001). It was significantly higher in EGC compared to high-risk (post-hoc Bonferroni, p=0.041) and normal (p<0.001). Itwas also higher in AGC compared with high-risk (p<0.001) and normal (p<0.001) groups. However, no significant difference wasfound between cancer groups. Blood ADAM 8 was correlated with N-stage (Spearman’s correlation, γs=0.320, p=0.011), but notwith T-stage or M-stage. Pearson’s correlations showed blood ADAM 8 was closely correlated with pre-inflammatory cytokines,IL-23 (p=0.036) and SDF-1α/CXCL12 (p=0.037); however, it was not correlated with pro-angiogenic cytokine IL-8 (p=0.313), andsCD40L (p=0.702). ROC curve and logistic regression demonstrated that blood ADAM 8 showed higher diagnostic accuracy (sensitivity,73.7%; specificity, 86.2%) than CEA (sensitivity, 23.1%; specificity, 91.4%). Combination of ADAM 8 and CEA further increasedthe diagnostic accuracy to predict GC (sensitivity, 81.8%; specificity, 84.0%). Conclusion: Blood ADAM 8 is a promising biomarker for early detection of GC.
