Biological copper levels in oral squamous cell carcinoma: A meta-analysis with insights into disease progression and prognosis.

BACKGROUND

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.

AIM

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.

METHOD

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.

RESULTS

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.

CONCLUSION

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.