Masato Fujiyoshi1, Atsushi Kuno2, Masanori Gotoh2, Moto Fukai3, Hideki Yokoo1, Hirofumi Kamachi1, Toshiya Kamiyama1, Masaaki Korenaga4, Masashi Mizokami4, Hisashi Narimatsu2, Akinobu Taketomi5. 1. Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan. 2. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, 305-8568, Japan. 3. Department of Transplant Surgery, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan. 4. Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, 272-8516, Japan. 5. Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Kita 15-jo Nishi 7-chome Kita-ku, Sapporo, 060-8638, Japan. taketomi@med.hokudai.ac.jp.
Abstract
BACKGROUND: Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+)-M2BP) is a novel serum marker of liver fibrosis identified in glycoproteomic biomarker screening studies, and its clinicopathological characteristics have yet to be elucidated sufficiently for clinical utilization. METHODS: We retrospectively analyzed the clinicopathology data and serum WFA(+)-M2BP levels in 376 hepatocellular carcinoma patients undergoing liver surgery. WFA(+)-M2BP was quantified in frozen serum samples collected at the time of surgery using the FastLec-Hepa method. RESULTS: Significant independent determinants of serum WFA(+)-M2BP levels included pathological diagnosis of cirrhosis, female gender, hepatitis C virus (HCV) infection, and liver dysfunction characteristics, such as abnormal indocyanine green retention rate at 15 min, platelet counts, albumin levels, alanine aminotransferase levels, and total bilirubin levels. Serum WFA(+)-M2BP levels increased with the pathological fibrosis stage and liver dysfunction severity. HCV infection significantly affected serum WFA(+)-M2BP levels throughout the pathological and functional progression of liver fibrosis, and the effect of gender was significant only in F4 stage patients with severe liver dysfunction. The diagnostic thresholds for cutoff index values for cirrhosis were 1.435 and 4.615 in HCV-negative and HCV-positive patients, respectively. Serum WFA(+)-M2BP levels at the time of operation were a significant predictor of hepatocellular carcinoma recurrence and overall survival in both HCV-negative and HCV-positive patients. CONCLUSIONS: Serum WFA(+)-M2BP levels reflected both the pathological and functional progression of liver fibrosis comprehensively and continuously. Elevated WFA(+)-M2BP levels were a significant risk factor for tumor recurrence and decreased overall survival after liver surgery independent of HCV infection.
BACKGROUND:Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA(+)-M2BP) is a novel serum marker of liver fibrosis identified in glycoproteomic biomarker screening studies, and its clinicopathological characteristics have yet to be elucidated sufficiently for clinical utilization. METHODS: We retrospectively analyzed the clinicopathology data and serum WFA(+)-M2BP levels in 376 hepatocellular carcinomapatients undergoing liver surgery. WFA(+)-M2BP was quantified in frozen serum samples collected at the time of surgery using the FastLec-Hepa method. RESULTS: Significant independent determinants of serum WFA(+)-M2BP levels included pathological diagnosis of cirrhosis, female gender, hepatitis C virus (HCV) infection, and liver dysfunction characteristics, such as abnormal indocyanine green retention rate at 15 min, platelet counts, albumin levels, alanine aminotransferase levels, and total bilirubin levels. Serum WFA(+)-M2BP levels increased with the pathological fibrosis stage and liver dysfunction severity. HCV infection significantly affected serum WFA(+)-M2BP levels throughout the pathological and functional progression of liver fibrosis, and the effect of gender was significant only in F4 stage patients with severe liver dysfunction. The diagnostic thresholds for cutoff index values for cirrhosis were 1.435 and 4.615 in HCV-negative and HCV-positive patients, respectively. Serum WFA(+)-M2BP levels at the time of operation were a significant predictor of hepatocellular carcinoma recurrence and overall survival in both HCV-negative and HCV-positive patients. CONCLUSIONS: Serum WFA(+)-M2BP levels reflected both the pathological and functional progression of liver fibrosis comprehensively and continuously. Elevated WFA(+)-M2BP levels were a significant risk factor for tumor recurrence and decreased overall survival after liver surgery independent of HCV infection.
Authors: Omid Haji-Ghassemi; Michel Gilbert; Jenifer Spence; Melissa J Schur; Matthew J Parker; Meredith L Jenkins; John E Burke; Henk van Faassen; N Martin Young; Stephen V Evans Journal: J Biol Chem Date: 2016-09-06 Impact factor: 5.157