Diagnostic accuracy of midkine on hepatocellular carcinoma: A meta-analysis

Abstract

ObjectiveTo evaluate the dependability and accuracy of midkine (MK) in the diagnosis of hepatocellular carcinoma (HCC).MethodsPubMed, EMBASE, Web of Science, China Biology Medicine disc and grey literature sources were searched from the date of database inception to January 2019. Two authors (B-H.Z. and B.L.) independently extracted the data and evaluated the study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR−) were estimated using a bivariate model. Moreover, hierarchical summary receiver operating characteristic curves were generated. The diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled using a univariate model.ResultsNine articles (11 studies) were included (1941 participants). The bivariate analysis revealed that the sensitivity and specificity of MK for HCC diagnosis were 0.85 (95% CI 0.78–0.91) and 0.83 (95% CI 0.76–0.88), respectively. We also found a LR+ of 5.05 (95% CI 3.33–7.40), a LR− of 0.18 (95% CI 0.11–0.28), a DOR of 31.74 (95% CI 13.98–72.09) and an AUC of 0.91 (95% CI 0.84–0.99). Subgroup analyses showed that MK provided the best efficiency for HCC diagnosis when the cutoff value was greater than 0.5 ng/mL.ConclusionsMK has an excellent diagnostic value for hepatocellular carcinoma.

A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis

“…Derivation of PLSec as a blood-based long-term HCC risk biomarker Our computational pipeline identified 43 candidate serum proteins for which validated antibodies are available for quantitative multiplex assessment (Figure 1). This preliminary panel included proteins that were previously reported as potential HCC risk biomarkers(e.g., interleukin-6 [IL-6], osteopontin, and midkine), [14][15][16] supporting the validity of our unbiased secretome biomarker derivation pipeline. Based on the association with the prognostic tissue transcriptome and the least information redundancy among the probes in the optimization set, we ultimately selected 6 highrisk-associated serum proteins, including vascular cell adhesion molecule 1 (VCAM-1), insulin-like growth factor-binding protein 7 (IGFBP-7), gp130, matrilysin, IL-6, and C-C motif chemokine ligand 21 (CCL-21), and 2 low-risk-associated serum proteins, angiogenin and protein S. We observed high within-plate reproducibility (r 2 = 0.9997, p = 1.1 3 10 À11 ), inter-plate/batch reproducibility (r 2 = 0.971, p = 7.7 3 10 À6 ) of technical replicates, and sensitivity for positive control proteins (99.9% G 2.5%), supporting the assay reliability as a clinical test.…”

Association between serum midkine levels and tumor size in Indonesian hepatocellular carcinoma patients: a cross-sectional study

“…A study by Zhang et al reported that midkine has a sensitivity of 85% and specificity of 83% in diagnosing HCC. This result was reported at a cut-off value of >0.5 ng/mL [34]. Another systematic review found that midkine is more superior compared to AFP in detecting HCC.…”

“…Midkine, a protein-secreting cytokine that is highly expressed in inflammation and cell proliferation, can be a diagnostic marker [29]. Detection of overexpressed Midkine in blood serum or plasma would adequately serve as early malignancy screening [30]. Previous studies observed that serum Midkine measures have higher sensitivity in the early stages of HCC than often-used measures [31].…”

Multi-omics analysis of pyroptosis regulation patterns and characterization of tumor microenvironment in patients with hepatocellular carcinoma

“…It has been reported that MDK also plays a role in the occurrence, development, metastasis, and prognosis of liver cancer ( Muramatsu, 2010 ). Further more, some studies have found that the sensitivity of MDK for the diagnosis of HCC could reach 85% through meta-analysis ( Zhang et al, 2019 ), and other studies have shown that the sensitivity can reach more than 80% in the early stages of liver cancer and AFP-negative liver cancer ( Luo et al, 2020 ). In addition, many liver cancers are associated with HBV and HCV infections, and it has been suggested that MDK may have an impact on hepatitis-associated HCC ( Lu et al, 2020 ).…”