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

Introduction To 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. Methods Relevant 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. Results Five 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). Conclusion Based on these findings, serum Midkine is a very promising diagnostic biomarker for AFP-negative HCC and should be validated further in large cohort studies.