Diagnostic value of combined detection of CA72-4, CA19-9, and carcinoembryonic antigen comparing to CA72-4 alone in gastric cancer: a systematic review and meta-analysis

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in humans. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA72-4 are all serum tumor markers for diagnosis of gastric cancer. However, the results of studies reporting the diagnosis of the combined three varied. In this study, the combined diagnostic performance of these 3 serum tumor markers was systematically evaluated. METHODS: PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang data were searched for literature on serum tumor markers CEA, CA19-9, and CA72-4 in the diagnosis of gastric cancer. The inclusion criteria were designed according to the Participants, Intervention, Control, Outcomes, Study (PICOS) principles. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) scoring scale was used to assess the quality of the literature. After extracting the data, Stata 16.0 software was used for meta-analysis. RESULTS: A total of 10 articles were finally included, and a total of 6,574 patients participated in diagnosis, 3,077 for confirmed GC and 3,497 for non-GC respectively. Meta-analysis results showed that the diagnostic sensitivity of the combined diagnosis of the 3 tumor markers was 0.67 [95% confidence interval (CI): 0.54, 0.77], the specificity was 0.89 (95% CI: 0.82, 0.93), the positive likelihood ratio was 5.9 (95% CI: 3.5, 9.8), the negative likelihood ratio was 0.38 (95% CI: 0.27, 0.53), and the diagnostic odds ratio (DOR) was 16 (95% CI: 8, 32). The diagnostic sensitivity of CA72-4 diagnosis alone was 0.58 (95% CI: 0.40, 0.73), specificity was 0.86 (95% CI: 0.80, 0.90), the positive likelihood ratio was 4.0 (95% CI: 3.1, 5.1), the negative likelihood ratio was 0.49 (95% CI: 0.34, 0.71), and the DOR was 8 (95% CI: 5, 14). The area under the ROC curve (AUC) values of the combined three diagnosis and CA72-4 diagnosis alone were 0.87 (95% CI: 0.83, 0.89) and 0.84 (95% CI: 0.81, 0.87), respectively, the difference was statistically significant (Z=4.86, P<0.05). DISCUSSION: The combined use of the 3 tumor markers has higher sensitivity and specificity than single marker diagnosis in the diagnosis of gastric cancer.