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

Tomonari Shimagaki, Sachiyo Yoshio, Hironari Kawai, Yuzuru Sakamoto, Hiroyoshi Doi, Michitaka Matsuda, Taizo Mori, Yosuke Osawa, Moto Fukai, Takeshi Yoshida, Yunfei Ma, Tomoyuki Akita, Junko Tanaka, Akinobu Taketomi, Rikinari Hanayama, Tomoharu Yoshizumi, Masaki Mori, Tatsuya Kanto

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number15788
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Epidermal Growth Factor
Hepatocellular Carcinoma
Biomarkers
Serum
Chronic Hepatitis
Liver Cirrhosis
Prothrombin
Healthy Volunteers
milk fat globule
Fetal Proteins
Hepatectomy
Area Under Curve
Liver Diseases
Early Diagnosis
Enzyme-Linked Immunosorbent Assay
Survival

All Science Journal Classification (ASJC) codes

  • General

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Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma. / Shimagaki, Tomonari; Yoshio, Sachiyo; Kawai, Hironari; Sakamoto, Yuzuru; Doi, Hiroyoshi; Matsuda, Michitaka; Mori, Taizo; Osawa, Yosuke; Fukai, Moto; Yoshida, Takeshi; Ma, Yunfei; Akita, Tomoyuki; Tanaka, Junko; Taketomi, Akinobu; Hanayama, Rikinari; Yoshizumi, Tomoharu; Mori, Masaki; Kanto, Tatsuya.

In: Scientific reports, Vol. 9, No. 1, 15788, 01.12.2019.

Research output: Contribution to journalArticle

Shimagaki, T, Yoshio, S, Kawai, H, Sakamoto, Y, Doi, H, Matsuda, M, Mori, T, Osawa, Y, Fukai, M, Yoshida, T, Ma, Y, Akita, T, Tanaka, J, Taketomi, A, Hanayama, R, Yoshizumi, T, Mori, M & Kanto, T 2019, 'Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma', Scientific reports, vol. 9, no. 1, 15788. https://doi.org/10.1038/s41598-019-52356-6
Shimagaki, Tomonari ; Yoshio, Sachiyo ; Kawai, Hironari ; Sakamoto, Yuzuru ; Doi, Hiroyoshi ; Matsuda, Michitaka ; Mori, Taizo ; Osawa, Yosuke ; Fukai, Moto ; Yoshida, Takeshi ; Ma, Yunfei ; Akita, Tomoyuki ; Tanaka, Junko ; Taketomi, Akinobu ; Hanayama, Rikinari ; Yoshizumi, Tomoharu ; Mori, Masaki ; Kanto, Tatsuya. / Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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abstract = "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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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

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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