title: Serum profiling based on fucosylated glycoproteins for differentiating between chronic hepatitis B and hepatocellular carcinoma.
abstract: Chronic infection with hepatitis B virus (HBV) is associated with the majority of cases of hepatocellular carcinoma (HCC) in China. Despite this, there is no effective method for the early detection of HBV-induced liver cancer. Aberrant fucosylation is known to occur during the development of HCC. We, therefore, developed a method of applying matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze the relationship between aberrant fucosylation, tumor genesis and progression of HBV-associated HCC, and to establish proteomic profiling of serum for early diagnosis of HCC. The MALDI-TOF MS was based on Lens culinaris agglutinin (LCA) lectin magnetic beads and their affinity for separation. The method was applied initially to a 'training' cohort of 111 serum samples obtained from subjects in China with no liver disease (n=26), chronic hepatitis B without cirrhosis (n=21), HBV-infected cirrhosis (n=32), or HBV-infected HCC (n=32). In contrast to previous findings, the results of our profiling analysis demonstrated defucosylation on some of the glycoproteins involved in HCC. HCC was then diagnostically classified in a 'blind test' cohort (n=96). In this group we demonstrated that, HCC could be distinguished from all serum samples, HBV-associated chronic liver disease, and HBV-associated cirrhosis with a sensitivity/specificity of 70%/70%, 78%/74%, and 81%/82%, respectively. When combined with serum alpha-fetoprotein detection (AFP>20 ng/mL), the sensitivity/specificity improved to 78%/88%, 85%/88%, and 89%/91%, respectively. In conclusion, serum glycoprotein fucosylation abnormalities have diverse forms in patients with HCC. MALDI-TOF MS profiling of aberrant serum fucosylated glycoproteins distinguished HCC from controls with high accuracy.
authors.affiliation: Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China. pamperslj28@yahoo.cn
authors.forename: Jian
authors.initials: J
authors.lastname: Liao
authors.forename: Ruixiu
authors.initials: R
authors.lastname: Zhang
authors.forename: Haihua
authors.initials: H
authors.lastname: Qian
authors.forename: Lu
authors.initials: L
authors.lastname: Cao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Zhengfeng
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005260:Female; D005643:Fucose / Q000737:chemistry; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods*; D012680:Sensitivity and Specificity; D044967:Serum / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D006023:Glycoproteins; D005643:Fucose