Serum profiling based on fucosylated glycoproteins for differentiating between chronic hepatitis B and hepatocellular carcinoma

详细信息	查看全文 | 推荐本文 |

• 作者：Jian Liao^a ; ^b ; ^{pamperslj28@yahoo.cn} ; Ruixiu Zhang^a ; ^{crossecho@yahoo.com.cn} ; Haihua Qian^a ; ^{qhhlb@yahoo.com.cn} ; Lu Cao^a ; ^{caolu0909@yahoo.com.cn} ; Yu Zhang^a ; ^{oct0072004@yahoo.com.cn} ; Wen Xu^a ; ^{andrew_xw@hotmail.com} ; Jing Li^a ; ^{lijinggava5945@tom.com} ; Mengchao Wu^a ; ^{wumengchao@yahoo.com.cn} ; Zhengfeng Yin^a ; ^{yinzfk@yahoo.com.cn}
• 关键词：Hepatitis B virus ; Hepatocellular carcinoma ; Fucosylation ; MALDI-TOF MS profiling ; Defucosylation
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：6 April, 2012
• 卷：420
• 期：2
• 页码：308-314
• 文件大小：705 K

摘要

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 鈥榯raining鈥?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 鈥榖lind test鈥?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.