Diagnostic Value of CDO1 Promoter Methylation in Lung Cancer via Liquid Biopsy: A Systematic Review and Meta-Analysis.

Abstract

Objective: To evaluate cysteine dioxygenase 1 (CDO1) gene promoter methylation in circulating tumor DNA as a biomarker for the early diagnosis of lung cancer.

Methods: Data up to June 5, 2025, across electronic databases (PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure) were searched. The quality assessment tool for diagnostic accuracy studies-2 (QUADAS-2) checklist was used to assess the risk of bias in the incorporated studies. A random-effects model was employed to generate summary statistics for diagnostic accuracy, which included pooled sensitivity and specificity estimates, the diagnostic odds ratio (DOR), and a summary receiver operating characteristic curve. An exploration of heterogeneity sources was undertaken using meta-regression, followed by a sensitivity analysis to test the consistency of the results. Finally, Deek's funnel plot was generated to estimate publication bias, and the clinical feasibility was evaluated using Fagan's nomogram.

Results: Seven relevant studies were included in this meta-analysis. No major concerns regarding the quality risk of the included studies were observed. The pooled diagnostic sensitivity, specificity, and DOR values of the CDO1 promoter methylation for lung cancer were 0.63 (95% CI: 0.60-0.67), 0.78 (95% CI: 0.74-0.82), and 5.96 (95% CI: 4.06-8.74), respectively, and the area under curve was 0.7423. Statistical heterogeneity was observed in sensitivity (I² = 73%, p < 0.1), specificity (I² = 79.5%, p < 0.1), and DOR (I² = 42.9%, p < 0.1); however, variables such as the region, sample source, sample size, and detection method did not significantly affect heterogeneity (p > 0.05). The results were robust as the DOR was not overly influenced by the deletion of any single study. No publication bias was observed in this study (p = 0.74). Additionally, under a pre-test probability of 20%, the positive post-test probability of CDO1 promoter methylation in lung cancer was predicted to be 42%. PROSPERO CRD420251131665, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251131665.

Conclusion: The detection of CDO1 promoter methylation in biofluids represents a promising tool for the early diagnosis of lung cancer. Future studies should focus on improving detection methodologies and investigating combinational strategies with high accuracy.