Clinical Validation of ADAM9 as a Prognostic Biomarker in Oral Cancer

Oral cancer has a high incidence in Taiwan, and identifying prognostic biomarkers is crucial. This study investigated the role of a disintegrin and metalloprotease 9 (ADAM9) in oral cancer progression and outcomes. This study investigated ADAM9 protein expression in 353 oral cancer tissue specimens...

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Published inOral diseases
Main Authors Lu, Jeng‐Wei, Shih, Pei‐Chen, Chuang, Show‐Mei, Tu, Wan‐Jung, Tsai, Ming‐Heng, Tsai, Yun‐Jung, Lin, Shu‐Hui
Format Journal Article
LanguageEnglish
Published Denmark 16.06.2025
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ISSN1354-523X
1601-0825
1601-0825
DOI10.1111/odi.15383

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Abstract Oral cancer has a high incidence in Taiwan, and identifying prognostic biomarkers is crucial. This study investigated the role of a disintegrin and metalloprotease 9 (ADAM9) in oral cancer progression and outcomes. This study investigated ADAM9 protein expression in 353 oral cancer tissue specimens through immunohistochemical (IHC) analysis. The analysis revealed that, among the 353 patients, 21 (6%) exhibited low ADAM9 expression, while the remaining 332 patients (94%) showed high ADAM9 expression, which correlated with advanced T status, poor overall survival, and unfavorable prognosis. Kaplan-Meier analysis confirmed that higher ADAM9 expression predicted significantly worse survival. Univariate and multivariate analyses identified ADAM9, histological grade, and AJCC stage as independent prognostic factors. Functionally, ADAM9 silencing in SAS and OC2 cells inhibited invasion and migration, downregulating matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 14 (MMP14). siRNA-mediated ADAM9 knockdown also reduced cell viability and migration, as confirmed by cell counting kit-8 and transwell assays. The Cancer Genome Atlas (TCGA) analysis further revealed a positive correlation between ADAM9 mRNA levels and matrix metalloproteinase 2 (MMP2) or MMP14 expression in oral cancer patients. This study identifies ADAM9 as a key driver of oral cancer in a Taiwanese cohort and highlights its diagnostic and therapeutic potential.
AbstractList Oral cancer has a high incidence in Taiwan, and identifying prognostic biomarkers is crucial. This study investigated the role of a disintegrin and metalloprotease 9 (ADAM9) in oral cancer progression and outcomes. This study investigated ADAM9 protein expression in 353 oral cancer tissue specimens through immunohistochemical (IHC) analysis. The analysis revealed that, among the 353 patients, 21 (6%) exhibited low ADAM9 expression, while the remaining 332 patients (94%) showed high ADAM9 expression, which correlated with advanced T status, poor overall survival, and unfavorable prognosis. Kaplan-Meier analysis confirmed that higher ADAM9 expression predicted significantly worse survival. Univariate and multivariate analyses identified ADAM9, histological grade, and AJCC stage as independent prognostic factors. Functionally, ADAM9 silencing in SAS and OC2 cells inhibited invasion and migration, downregulating matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 14 (MMP14). siRNA-mediated ADAM9 knockdown also reduced cell viability and migration, as confirmed by cell counting kit-8 and transwell assays. The Cancer Genome Atlas (TCGA) analysis further revealed a positive correlation between ADAM9 mRNA levels and matrix metalloproteinase 2 (MMP2) or MMP14 expression in oral cancer patients. This study identifies ADAM9 as a key driver of oral cancer in a Taiwanese cohort and highlights its diagnostic and therapeutic potential.
Oral cancer has a high incidence in Taiwan, and identifying prognostic biomarkers is crucial. This study investigated the role of a disintegrin and metalloprotease 9 (ADAM9) in oral cancer progression and outcomes.BACKGROUNDOral cancer has a high incidence in Taiwan, and identifying prognostic biomarkers is crucial. This study investigated the role of a disintegrin and metalloprotease 9 (ADAM9) in oral cancer progression and outcomes.This study investigated ADAM9 protein expression in 353 oral cancer tissue specimens through immunohistochemical (IHC) analysis.METHODSThis study investigated ADAM9 protein expression in 353 oral cancer tissue specimens through immunohistochemical (IHC) analysis.The analysis revealed that, among the 353 patients, 21 (6%) exhibited low ADAM9 expression, while the remaining 332 patients (94%) showed high ADAM9 expression, which correlated with advanced T status, poor overall survival, and unfavorable prognosis. Kaplan-Meier analysis confirmed that higher ADAM9 expression predicted significantly worse survival. Univariate and multivariate analyses identified ADAM9, histological grade, and AJCC stage as independent prognostic factors. Functionally, ADAM9 silencing in SAS and OC2 cells inhibited invasion and migration, downregulating matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 14 (MMP14). siRNA-mediated ADAM9 knockdown also reduced cell viability and migration, as confirmed by cell counting kit-8 and transwell assays. The Cancer Genome Atlas (TCGA) analysis further revealed a positive correlation between ADAM9 mRNA levels and matrix metalloproteinase 2 (MMP2) or MMP14 expression in oral cancer patients.RESULTSThe analysis revealed that, among the 353 patients, 21 (6%) exhibited low ADAM9 expression, while the remaining 332 patients (94%) showed high ADAM9 expression, which correlated with advanced T status, poor overall survival, and unfavorable prognosis. Kaplan-Meier analysis confirmed that higher ADAM9 expression predicted significantly worse survival. Univariate and multivariate analyses identified ADAM9, histological grade, and AJCC stage as independent prognostic factors. Functionally, ADAM9 silencing in SAS and OC2 cells inhibited invasion and migration, downregulating matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 14 (MMP14). siRNA-mediated ADAM9 knockdown also reduced cell viability and migration, as confirmed by cell counting kit-8 and transwell assays. The Cancer Genome Atlas (TCGA) analysis further revealed a positive correlation between ADAM9 mRNA levels and matrix metalloproteinase 2 (MMP2) or MMP14 expression in oral cancer patients.This study identifies ADAM9 as a key driver of oral cancer in a Taiwanese cohort and highlights its diagnostic and therapeutic potential.CONCLUSIONSThis study identifies ADAM9 as a key driver of oral cancer in a Taiwanese cohort and highlights its diagnostic and therapeutic potential.
Author Chuang, Show‐Mei
Tsai, Ming‐Heng
Lin, Shu‐Hui
Shih, Pei‐Chen
Tsai, Yun‐Jung
Lu, Jeng‐Wei
Tu, Wan‐Jung
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  surname: Lu
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  organization: Department of Bioscience and Biotechnology National Taiwan Ocean University Keelung Taiwan, Biotech Research and Innovation Centre University of Copenhagen Copenhagen Denmark, The Finsen Laboratory, Rigshospitalet/National University Hospital, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark
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  organization: Institute of Biomedical Sciences National Chung Hsing University Taichung Taiwan
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  fullname: Chuang, Show‐Mei
  organization: Department of Post‐Baccalaureate Medicine National Chung Hsing University Taichung Taiwan, Graduate Institute of Clinical Nursing National Chung Hsing University Taichung Taiwan, Graduate Institute of Clinical Medicine National Chung Hsing University Taichung Taiwan, Department of law National Chung Hsing University Taichung Taiwan, Department of Surgical Pathology Yuanlin Christian Hospital Changhua Taiwan
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  organization: Department of Surgical Pathology Changhua Christian Hospital Changhua Taiwan
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  surname: Lin
  fullname: Lin, Shu‐Hui
  organization: Department of Surgical Pathology Changhua Christian Hospital Changhua Taiwan, Department of Medical Laboratory Science and Biotechnology Central Taiwan University of Science and Technology Taichung Taiwan, Department of Post‐Baccalaureate Medicine, College of Medicine National Chung Hsing University Taichung Taiwan
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ADAM9
immunohistochemistry
prognosis
oral cancer
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Snippet Oral cancer has a high incidence in Taiwan, and identifying prognostic biomarkers is crucial. This study investigated the role of a disintegrin and...
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Title Clinical Validation of ADAM9 as a Prognostic Biomarker in Oral Cancer
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