Serum Midkine for AFP-negative hepatocellular carcinoma diagnosis: a systematic review and meta-analysis

IntroductionTo date, alpha-feto protein (AFP) remains the most widely used serum biomarker for hepatocellular carcinoma (HCC) diagnosis and prognosis. However, its role has become controversial as close to 30% of early stage HCC patients are AFP negative. Different studies on the diagnostic performance of novel AFP-negative HCC biomarkers have shown inconsistent results of sensitivity, specificity, and area under the receiver operating curve (AUROC). Here, we conducted a systematic review and meta-analysis to resolve this inconsistency.MethodsRelevant studies were systematically searched from PubMed, Embase, Cochrane library, Scopus, and the China National Knowledge Infrastructure (chkd-cnki) databases up to the 20th October 2022. The Newcastle-Ottawa Scale was used to assess the methodological quality of included studies. Sensitivity, specificity, and area under the curve were pooled using the random effect model.ResultsFive studies, with a total of 286 patients, were included. Serum Midkine was assessed using enzyme-linked immunosorbent assay (ELISA) in all the studies, at diagnostic thresholds varying from 0.387 to 5.1 ng/ml. The summary estimates for serum Midkine were 76% (95% CI 70-81%) sensitivity, 85% (95% CI 82-87%) specificity, and 91% area under the receiver operating characteristic curve (AUC), while the pooled diagnostic odds ratio (DOR) was 27.64 (95% CI 4.95-154.17).ConclusionBased on these findings, serum Midkine is a very promising diagnostic biomarker for AFP-negative HCC and should be validated further in large cohort studies.