ADAM9作为口腔癌预后生物标志物的临床验证

IF 2.9 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Oral diseases Pub Date : 2025-06-16 DOI:10.1111/odi.15383
Jeng-Wei Lu, Pei-Chen Shih, Show-Mei Chuang, Wan-Jung Tu, Ming-Heng Tsai, Yun-Jung Tsai, Shu-Hui Lin
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引用次数: 0

摘要

背景:口腔癌在台湾的发病率很高,确定预后生物标志物至关重要。本研究探讨了崩解素和金属蛋白酶9 (ADAM9)在口腔癌进展和预后中的作用。方法:采用免疫组化(IHC)方法对353例口腔癌组织标本中ADAM9蛋白的表达进行检测。结果:分析显示,在353例患者中,21例(6%)ADAM9低表达,其余332例(94%)ADAM9高表达,与T状态晚期、总生存期差、预后不良相关。Kaplan-Meier分析证实,ADAM9表达越高,生存率越低。单因素和多因素分析发现,ADAM9、组织学分级和AJCC分期是独立的预后因素。在功能上,ADAM9沉默在SAS和OC2细胞中抑制侵袭和迁移,下调基质金属蛋白酶9 (MMP9)和基质金属蛋白酶14 (MMP14)。通过细胞计数试剂盒-8和transwell实验证实,sirna介导的ADAM9敲低也降低了细胞活力和迁移。Cancer Genome Atlas (TCGA)分析进一步揭示了ADAM9 mRNA水平与口腔癌患者基质金属蛋白酶2 (MMP2)或MMP14表达呈正相关。结论:本研究确定ADAM9是台湾人群口腔癌的关键驱动因素,并强调其诊断和治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical Validation of ADAM9 as a Prognostic Biomarker in Oral Cancer.

Background: 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.

Methods: This study investigated ADAM9 protein expression in 353 oral cancer tissue specimens through immunohistochemical (IHC) analysis.

Results: 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.

Conclusions: This study identifies ADAM9 as a key driver of oral cancer in a Taiwanese cohort and highlights its diagnostic and therapeutic potential.

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来源期刊
Oral diseases
Oral diseases 医学-牙科与口腔外科
CiteScore
7.60
自引率
5.30%
发文量
325
审稿时长
4-8 weeks
期刊介绍: Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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