TY - JOUR
T1 - Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma
AU - Shimagaki, Tomonari
AU - Yoshio, Sachiyo
AU - Kawai, Hironari
AU - Sakamoto, Yuzuru
AU - Doi, Hiroyoshi
AU - Matsuda, Michitaka
AU - Mori, Taizo
AU - Osawa, Yosuke
AU - Fukai, Moto
AU - Yoshida, Takeshi
AU - Ma, Yunfei
AU - Akita, Tomoyuki
AU - Tanaka, Junko
AU - Taketomi, Akinobu
AU - Hanayama, Rikinari
AU - Yoshizumi, Tomoharu
AU - Mori, Masaki
AU - Kanto, Tatsuya
N1 - Funding Information:
This research has been funded by the Program for Basic and Clinical Research on Hepatitis (AMED) (JP18fk0210022 and JP18fk0320041) and the National Center for Global Health and Medicine (29-shi-1007). Tatsuya Kanto received lecture fees from Gilead Scienes, Merk Sharp & Dohme. In addition, other authors have no competing interests as defined by Nature Research, or other interests that might be perceived to influence the results and/or discussion reported in this paper.
Funding Information:
The study protocol conformed to the ethical guidelines for human clinical research established by the Japanese Ministry of Health, Labor and Welfare and was approved by the ethics committee at Kyushu University, Hokkaido University and the National Center for Global Health and Medicine. Written informed consent was obtained from all patients at enrollment.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-019-52356-6
DO - 10.1038/s41598-019-52356-6
M3 - Article
C2 - 31673081
AN - SCOPUS:85074293437
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 15788
ER -