血清生物标志物对原发性肝癌早期诊断价值的Meta分析OA

Objective:To explore and compare the diagnostic accuracy of ten serum biomarkers including alpha-fetopro-tein(AFP)and protein induced by vitamin K absence or antagonist-II(PIVKA-II)when used alone for the early diagnosis of primary liver cancer(PLC),so as to provide evidence-based basis for the selection and combined application of biomark-ers in the early screening of high-risk populations.Methods:Computerized searches were performed in PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Data,VIP and CBM databases to collect diagnostic accuracy studies on serum biomarkers for early PLC published between January 2021 and January 2026.Two researchers independently screened the literature,extracted data,and assessed study quality using the Newcastle-Ottawa Scale.A Meta-analysis of diagnostic test accuracy(DTA)was performed using Stata/MP 19.5.Based on the mean±standard deviation and clinically common diagnostic cut-off values from each included study,2×2 contingency tables were established to calculate the pooled sensitivity(Sn),pooled specificity(Sp),AUC,and corresponding 95%CI of each biomarker.The I2 statistic was adopted to evaluate between-study heterogeneity.Results:A total of 33 studies(20 published in Chinese and 13 in English)were included,in-volving 2,927 patients with early-stage PLC and 2,590 control subjects.The DTA Meta-analysis showed that all 10 biomarkers had diagnostic value for early PLC:AFP(pooled Sn=0.81,pooled Sp=0.80,AUC=0.87),PIVKA-II(pooled Sn=0.93,pooled Sp=0.87,AUC=0.96),gamma-glutamyl transferase(GGT)(pooled Sn=0.90,pooled Sp=0.82,AUC=0.93),GGT/alanine aminotransferase(ALT)(pooled Sn=0.94,pooled Sp=0.85,AUC=0.96),glypican-3(pooled Sn=0.85,pooled Sp=0.91,AUC=0.94),des-gamma-carboxy prothrombin(DCP)(pooled Sn=0.87,pooled Sp=0.94,AUC=0.96),Golgi protein 73(pooled Sn=0.89,pooled Sp=0.90,AUC=0.94),alpha-fetopro-tein Lens culinaris agglutinin-reactive fraction(AFP-L3%)(pooled Sn=0.87,pooled Sp=0.95,AUC=0.96),carbohy-drate antigen 19-9(CA19-9)(pooled Sn=0.94,pooled Sp=0.97,AUC=0.98),and microRNA(pooled Sn=0.82,pooled Sp=0.82,AUC=0.89)(all P<0.01).Except for AFP(I2=70.52%)and CA19-9(I2=78.33%),the pooled I2 values of the other eight biomarkers were all≤50%,suggesting acceptable heterogeneity;after subgroup analyses of AFP and CA19-9 stratified by control type,the I2 within each subgroup decreased to less than 50%.Sensitivity analysis indicated that the results for major biomarkers such as AFP and PIVKA-II were robust.The Deeks'funnel plot indicated no significant publication bias among studies evaluating AFP(P=0.230).Conclusion:Multiple serum biomarkers have value for the early diagnosis of PLC.Among them,PIVKA-II,GGT/ALT,DCP,AFP-L3%and CA19-9 show better and more robust diagnostic performance than conventional AFP.Given the limited diagnostic performance of single biomarkers,combined testing of multi-ple biomarkers is clinically recommended to boost early diagnostic performance.