A Disintegrin and Metalloproteinase 8 as a Potential Blood Biomarker for Early Diagnosis of Gastric Cancer

PURPOSE: We aimed to evaluate the clinical significance of a disintegrin and metalloproteinase 8 (ADAM 8) as a potential blood biomarker for gastric cancer (GC). MATERIALS AND METHODS: Blood ADAM 8 was measured by ELISA. Cytokines/chemokines [interleukin-23 (IL-23), stromal cell-derived factor 1α/CXC chemokine ligand 12 (SDF-1α/CXCL12), interleukin-8 (IL-8), and soluble CD40 ligand (sCD40L)] were measured by 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 their correlations with blood ADAM 8. To evaluate the diagnostic accuracy to predict GC, receiver operating characteristic (ROC) curve and 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). It was also higher in AGC compared with high-risk (p<0.001) and normal (p<0.001) groups. However, no significant difference was found between cancer groups. Blood ADAM 8 was correlated with N-stage (Spearman's correlation, γs=0.320, p=0.011), but not with 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), and sCD40L (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 increased the diagnostic accuracy to predict GC (sensitivity, 81.8%; specificity, 84.0%). CONCLUSION: Blood ADAM 8 is a promising biomarker for early detection of GC.

Value of Combined Determination of Plasma M2-PK, Serum CEA and ADAM8 in the Diagnosis of Non-small Cell Lung Cancer / 医学研究杂志

Objective To study the clinical application value of plasma M2 pyruvate kinase (M2-PK),serum tumor marker carcinoembryonic antigen (CEA) and serum level of integrin-like protein-8 (ADAM8) in the diagnosis of Non-small cell lung cancer (NSCLC).Methods Seventy-five patients with NSCLC admitted to our hospital from April 2014 to August 2016 were randomly selected as study group.Seventy-five healthy subjects were randomly selected as control group.Serum ADAM8 and M2-PK levels were measured by enzyme-linked immunosorbent assay (ELISA) in all subjects,and serum CEA levels were determined by electrochemiluminescence (ECLIA).The clinical value of M2-PK,CEA and ADAM8 in diagnosis of NSCLC were analyzed by ROC curve.Results The levels of M2-PK,CEA and ADAM8 in the study group were significantly higher than those in the control group (P ＜ 0.05).The levels of M2-PK and CEA in patients with adenocarcinoma were significantly higher than those in squamous cell carcinoma patients (P ＜0.05),and the levels of M2-PK,CEA and ADAM8 in stage Ⅲ-Ⅳ patients were significantly higher than those in stage Ⅰ-Ⅱ patients (P ＜ 0.05).The AUC of M2-PK,CEA and ADAM8 combined detection (0.924) was significantly higher than that of M2-PK,CEA and ADAM8 separate detection (0.731,0.858 and 0.790),and the difference was statistically significant (P ＜ 0.05).The sensitivity and specificity of M2-PK,CEA and ADAM8 combined detection were significantly higher than those of M2-PK,CEA and ADAM8 separate detection (P ＜ 0.05).Conclusion The value of M2-PK,CEA and ADAM8 in diagnosing NSCLC has a certain clinical value,and the diagnostic value of M2-PK,CEA and ADAM8combined detection is superior to that of separate detection,and M2-PK,CEA and ADAM8 combined detection worthy of clinical application.

Expression of ADAM8 in hepatocellular carcinoma and its clinical significance / 中华肝胆外科杂志

Objective To investigate the expression of ADAM8 in patients with hepatocellular carcinoma (HCC) and its clinical significance.Methods The protein expression of ADAM8 in HCC tissues was analyzed using immunohistochemical analysis.Serum levels of ADAM8 were measured by ELISA in 126 patients with HCC,50 patients with liver cirrhosis (LC) and 50 healthy individuals.The relationship between patients' pathological features and serum ADAM8 level was analyzed.Results Immunohistochemical analysis showed that ADAM8 expression was associated closely with serum AFP elevation,tumor size,histological differentiation,and tumor stage.The ELISA assay showed that the serum levels of ADAM8 in the HCC were significantly higher than those in LC and healthy groups.Kaplan-Meier survival analysis showed that high expression of serum ADAM8 exhibited a significant correlation with poor prognosis for HCC patients.Multivariate analysis revealed that serum ADAM8 expression is an independent prognostic parameter for the overall survival rate of HCC patients.Conclusion ADAM8 expression was closely associated with tumor size,serum AFP elevation,tumor differentiation,tumor stage and prognosis in hepatocellular carcinoma.Therefore,ADAM8 expression may serve as a biomarker for predicting the prognosis of patients in hepatocellular carcinoma.

Reduced expression of ADAM8 and its role in breast cancer / 中华内分泌外科杂志

ObjectiveTo investigate the expression of a disintegrin-like and metalloproteinase 8 ( ADAM8 ) in breast cancer and in normal breast tissues and its negative regulation role in tumorigenesis and progress of breast cancer.MethodsThe expression of ADAM8 in breast cancer and normal breast tissues was detected by immunohistochemistry (IHC),qRT-PCR,and Western blot.The relation between ADAM8 expression and the clinicopathological parameters of breast cancer patients was analyzed.ResultsADAM8 was expressed in breast cancer and normal breast tissues.The expression of ADAM8 mRNA and protein was significantly lower in breast cancer than in normal breast tissues (qRT-PCR:P =0.015,IHC:P =0.044,Western blot:P =0.000).The expression rate of ADAM8 was related to lymph node metastasis,tumor stage and tumor size,although the difference had no statistical significance.IHC results showed that ADAM8 expression level was lower in stage Ⅲ + Ⅳthan in stage Ⅰ + Ⅱ ( P =0.574 ).qRT-PCR showed ADAM8 mRNA expression was lower in stage Ⅱb + Ⅲ than in stage Ⅰ + Ⅱ a ( P =0.247).ADAM8 expression was lower in the breast cancer tissues with lymph node metastasis than in those without lymph node metastasis (P =0.560 by IHC and P =0.592 by qRT-PCR).ADAM8 expression was lower in tumors whose size ＞ 2 cm than in tumors whose size ≤ 2 cm,however,the difference had no statistical significance ( P ＞ 0.05 ).ConclusionsADAM8 is significantly lower-expressed in breast cancer than in normal breast tissues,which is associated with clinical stages and lymph node metastasis.The reduced expression of ADAM8 may play a role in the pathogenesis and progress of breast cancer.