Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma

Sci Rep. 2019 Oct 31;9(1):15788. doi: 10.1038/s41598-019-52356-6.


Current serum hepatocellular carcinoma (HCC) biomarkers are insufficient for early diagnosis. We aimed to clarify whether serum MFG-E8 can serve as a diagnostic or prognostic biomarker of HCC. Serum MFG-E8 levels of 282 HCC patients, who underwent primary hepatectomy, were examined by ELISA. We also quantified serum MFG-E8 levels in patients with chronic hepatitis (CH), liver cirrhosis (LC), as well as in healthy volunteers (HVs). Serum MFG-E8 levels were significantly lower in HCC patients than in HVs regardless of the etiology of liver disease (3.6 ± 0.1 vs 5.8 ± 0.2 ng/mL, p < 0.0001), and recovered after treatment of HCC. Serum MFG-E8 levels in CH and LC patients were comparable to those in HVs. Serum MFG-E8 could detect HCCs, even α-fetoprotein (AFP)-negative or des-γ-carboxy prothrombin (DCP)-negative HCCs, in CH and LC patients. Our new HCC prediction model using MFG-E8 and DCP (Logit(p) = 2.619 - 0.809 × serum MFG-E8 + 0.0226 × serum DCP) distinguished HCC patients from CH and LC patients with an area under the curve of 0.923, a sensitivity of 81.1%, and a specificity of 89.8%. Futhermore, low preoperative serum MFG-E8 was an independent predictor of poor overall survival. Thus, serum MFG-E8 could serve as a feasible diagnostic and prognostic biomarker for HCC.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Surface / blood*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / secondary
  • Male
  • Middle Aged
  • Milk Proteins / blood*
  • Neoplasm Proteins / blood*
  • Preoperative Care*
  • Prospective Studies
  • Survival Rate


  • Antigens, Surface
  • Biomarkers, Tumor
  • MFGE8 protein, human
  • Milk Proteins
  • Neoplasm Proteins