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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/CX...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Yonsei University College of Medicine
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660445/ https://www.ncbi.nlm.nih.gov/pubmed/31347325 http://dx.doi.org/10.3349/ymj.2019.60.8.713 |
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author | Chung, Hye Won Kim, Jin Ju Choi, Jae Il Lee, Hae Rim Lim, Jong-Baeck |
author_facet | Chung, Hye Won Kim, Jin Ju Choi, Jae Il Lee, Hae Rim Lim, Jong-Baeck |
author_sort | Chung, Hye Won |
collection | PubMed |
description | 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, γ(s)=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. |
format | Online Article Text |
id | pubmed-6660445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Yonsei University College of Medicine |
record_format | MEDLINE/PubMed |
spelling | pubmed-66604452019-08-01 A Disintegrin and Metalloproteinase 8 as a Potential Blood Biomarker for Early Diagnosis of Gastric Cancer Chung, Hye Won Kim, Jin Ju Choi, Jae Il Lee, Hae Rim Lim, Jong-Baeck Yonsei Med J Original Article 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, γ(s)=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. Yonsei University College of Medicine 2019-08-01 2019-07-19 /pmc/articles/PMC6660445/ /pubmed/31347325 http://dx.doi.org/10.3349/ymj.2019.60.8.713 Text en © Copyright: Yonsei University College of Medicine 2019 https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Chung, Hye Won Kim, Jin Ju Choi, Jae Il Lee, Hae Rim Lim, Jong-Baeck A Disintegrin and Metalloproteinase 8 as a Potential Blood Biomarker for Early Diagnosis of Gastric Cancer |
title | A Disintegrin and Metalloproteinase 8 as a Potential Blood Biomarker for Early Diagnosis of Gastric Cancer |
title_full | A Disintegrin and Metalloproteinase 8 as a Potential Blood Biomarker for Early Diagnosis of Gastric Cancer |
title_fullStr | A Disintegrin and Metalloproteinase 8 as a Potential Blood Biomarker for Early Diagnosis of Gastric Cancer |
title_full_unstemmed | A Disintegrin and Metalloproteinase 8 as a Potential Blood Biomarker for Early Diagnosis of Gastric Cancer |
title_short | A Disintegrin and Metalloproteinase 8 as a Potential Blood Biomarker for Early Diagnosis of Gastric Cancer |
title_sort | disintegrin and metalloproteinase 8 as a potential blood biomarker for early diagnosis of gastric cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660445/ https://www.ncbi.nlm.nih.gov/pubmed/31347325 http://dx.doi.org/10.3349/ymj.2019.60.8.713 |
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