Glycosylation patterns and PHA-E-associated glycoprotein profiling associated with early hepatic encephalopathy in Chinese hepatocellular carcinoma patients.
Hepatic encephalopathy (HE) as a severe neuropsychiatric complication is commonly present in the end stage of Hepatocellular Carcinoma (HCC). However, widely accepted biomarkers for diagnosing early HE are still absent. Here, we screened glycosylation patterns of serum proteins from Chinese HCC patients with or without early HE by lectin microarray. Then, phaseolus vulgaris erythroagglutinin (PHA-E) as a lectin binding with bisecting GlcNAc structure which was significantly decreased in sera from Chinese HCC patients with early HE, was chosen to perform lectin affinity chromatography, following by in-gel digestion, Mass Spectrometry (MS) analysis and bioinformatics analysis. Here we found, 13 lectins showed statistically significant reduction suggesting GalNAc, terminal α-1,3 Man, bisecting GlcNAc, (GlcNAc)n, O-GlcNAc, Neu5Ac, tetra-antennary complex-type N-glycan and GalNAc α/β1-3/6 Gal were decreased in serum glycoproteins from Chinese HCC patients with early HE. Furthermore, a total of 141 PHA-E-associated glycoproteins were identified in MS, of which 12 serum glycoproteins only in Chinese HCC patients without early HE and 26 serum glycoproteins only in Chinese HCC patients with early HE. In addition, bioinformatics analysis revealed the PHA-E-associated serum glycoproteins only in Chinese HCC patients with early HE might be related to early HE occurrence through p38 MAPK signaling pathway and MAPK/ERK signaling pathway. Collectively, this was the first glycomics study of serum proteins in HCC patients with early HE and it could provide a database for discovering and developing serum biomarkers to identify and predict early HE in HCC patients.
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationShanghai, China; Cancer Research Center, Institutes of Biomedical Sciences, Fudan UniversityShanghai, China.
Tian-Hua
TH
Liu
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University Nanning, Guangxi, China.
Deng-He
DH
Liu
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University Nanning, Guangxi, China.
Cui-Ju
CJ
Mo
Cancer Research Center, Institutes of Biomedical Sciences, Fudan University Shanghai, China.
Lu
L
Sun
Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200032, China.
Xiao-Xia
XX
Liu
Cancer Research Center, Institutes of Biomedical Sciences, Fudan University Shanghai, China.
Wei
W
Li
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education Shanghai, China.
Shu
S
Zhang
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationShanghai, China; Cancer Research Center, Institutes of Biomedical Sciences, Fudan UniversityShanghai, China.
Yin-Kun
YK
Liu
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education Shanghai, China.
Kun
K
Guo
Hepatocellular carcinoma; LC-MS/MS; glycoproteomics; hepatic encephalopathy; lectin microarray; lectin-affinity chromatography