Gastric cancer detection based on cell-free DNA in blood: A systematic review and meta-analysis

Objective: Screening and early diagnosis of gastric cancer (GC) are crucial for improved prognosis. However, gastroscopic screening is not feasible in large populations due to its high cost and invasive nature. The detection of circulating cell-free DNA (cfDNA) provides an attractive minimally-invasive alternative for screening of GC. In this systematic review and meta-analysis, we evaluate the diagnostic value of cfDNA-based markers for GC, including the detection of total concentration, mutations, and methylation alterations. Methods: We performed a systematic search of four literature databases (PubMed, Embase, Web of Science, and Cochrane Library) for articles published before November 2022. The revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of included studies. PROSPERO registration number: CRD42021210830. Results: A total of 15 original articles involving 2849 individuals were included in this meta-analysis, comprising five studies on concentration, nine studies on methylation alterations, and one study on mutation biomarkers of cfDNA. Among these studies, seven selected early-stage GC subjects. For the diagnoses of overall stages and early-stage GC, the pooled sensitivities with 95% confidence interval were 0.74 (0.66–0.82) and 0.64 (0.51–0.76), and the pooled specificities were 0.92 (0.84–0.96) and 0.94 (0.87–0.98) with summary areas under the curve (SAUCs) of 0.89 (0.86–0.91) and 0.86 (0.83–0.89), respectively. Conclusions: This meta-analysis suggests that cfDNA-based biomarkers show diagnostic value for GC early detection.