Sundar Sandhya, Pandiar Deepak, Yuwanati Monal
Dept. of Oral Pathology and Microbiology, Saveetha Dental College & Hospitals, Saveetha institute of Medical and Technical Sciences, Chennai, 600077, Tamilnadu, India.
J Oral Biol Craniofac Res. 2025 Sep-Oct;15(5):1010-1020. doi: 10.1016/j.jobcr.2025.07.003. Epub 2025 Jul 15.
Oral squamous cell carcinoma (OSCC) is a common, aggressive cancer characterized by frequent local invasion, metastasis, and recurrence. Previous research has reported altered copper levels in OSCC; however, studies employed different methods to assess these levels, leading to inconsistent or inaccurate measurements. This variability impacts the evaluation of copper's potential as a biomarker in OSCC.
This systematic review and meta-analysis aimed to evaluate copper concentrations in serum, saliva, and tissue of OSCC patients compared to healthy controls and explore its potential association with disease progression and prognosis.
ologyA comprehensive search across electronic databases identified 147 studies, with 18 meeting the inclusion criteria following full-text screening. Data from 751 OSCC patients and 628 healthy controls were analysed. A random-effects meta-analysis was employed to compute standardized mean differences (SMD). Subgroup analyses based on sample type and analytical technique were performed. Risk of bias was assessed using established quality checklists.
Serum copper levels were significantly higher in OSCC patients (SMD: 2.22 μg/ml; I = 98 %), with improved effect size (SMD: 2.71 μg/ml) after excluding high-risk studies. Salivary copper levels were also elevated (SMD: 0.49 μg/ml), increasing further upon sensitivity analysis (SMD: 0.75 μg/ml; p = 0.02). One study showed markedly higher copper in tumor tissue. Studies using ICP-OES showed lower heterogeneity. No conclusive evidence linked copper levels to clinical outcomes.
Copper concentrations are significantly elevated in OSCC across serum and saliva. However, current evidence does not support its role as a prognostic biomarker. Standardized, prospective studies are warranted.
口腔鳞状细胞癌（OSCC）是一种常见的侵袭性癌症，其特征是频繁发生局部侵袭、转移和复发。先前的研究报道了OSCC中铜水平的改变；然而，这些研究采用了不同的方法来评估这些水平，导致测量结果不一致或不准确。这种变异性影响了对铜作为OSCC生物标志物潜力的评估。
本系统评价和荟萃分析旨在评估与健康对照相比，OSCC患者血清、唾液和组织中的铜浓度，并探讨其与疾病进展和预后的潜在关联。
通过对电子数据库进行全面检索，共识别出147项研究，经过全文筛选后，有18项符合纳入标准。对来自751例OSCC患者和628例健康对照的数据进行了分析。采用随机效应荟萃分析来计算标准化平均差（SMD）。基于样本类型和分析技术进行了亚组分析。使用既定的质量检查表评估偏倚风险。
OSCC患者的血清铜水平显著更高（SMD：2.22μg/ml；I² = 98%），排除高风险研究后效应量有所改善（SMD：2.71μg/ml）。唾液铜水平也有所升高（SMD：0.49μg/ml），敏感性分析后进一步升高（SMD：0.75μg/ml；p = 0.02）。一项研究显示肿瘤组织中的铜含量明显更高。使用电感耦合等离子体质谱法（ICP-OES）的研究显示异质性较低。没有确凿证据表明铜水平与临床结局有关。
OSCC患者血清和唾液中的铜浓度显著升高。然而，目前的证据不支持其作为预后生物标志物的作用。有必要进行标准化的前瞻性研究。
