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Heterogeneities of Site-Specific N-Glycosylation in HCC Tumors With Low and High AFP Concentrations
- Source :
- Frontiers in Oncology, Vol 10 (2020)
- Publication Year :
- 2020
- Publisher :
- Frontiers Media S.A., 2020.
-
Abstract
- Hepatocellular carcinoma (HCC) is still one of the malignant tumors with high morbidity and mortality in China and worldwide. Although alpha-fetoprotein (AFP) as well as core fucosylated AFP-L3 have been widely used as important biomarkers for HCC diagnosis and evaluation, the AFP level shows a huge variation among HCC patient populations. In addition, the AFP level has also been proved to be associated with pathological grade, progression, and survival of HCC patients. Understanding the intrinsic heterogeneities of HCC associated with AFP levels is essential for the molecular mechanism studies of HCC with different AFP levels as well as for the potential early diagnosis and personalized treatment of HCC with AFP negative. In this study, an integrated N-glycoproteomic and proteomic analysis of low and high AFP levels of HCC tumors was performed to investigate the intrinsic heterogeneities of site-specific glycosylation associated with different AFP levels of HCC. By large-scale profiling and quantifying more than 4,700 intact N-glycopeptides from 20 HCC and 20 paired paracancer samples, we identified many commonly altered site-specific N-glycans from HCC tumors regardless of AFP levels, including decreased modifications by oligo-mannose and sialylated bi-antennary glycans, and increased modifications by bisecting glycans. By relative quantifying the intact N-glycopeptides between low and high AFP tumor groups, the great heterogeneities of site-specific N-glycans between two groups of HCC tumors were also uncovered. We found that several sialylated but not core fucosylated tri-antennary glycans were uniquely increased in low AFP level of HCC tumors, while many core fucosylated bi-antennary or hybrid glycans as well as bisecting glycans were uniquely increased in high AFP tumors. The data provide a valuable resource for future HCC studies regarding the mechanism, heterogeneities and new biomarker discovery.
- Subjects :
- 0301 basic medicine
Cancer Research
Glycan
Glycosylation
Personalized treatment
site-specific glycosylation
lcsh:RC254-282
03 medical and health sciences
High morbidity
chemistry.chemical_compound
alpha-fetoprotein
0302 clinical medicine
N-linked glycosylation
medicine
Biomarker discovery
neoplasms
mass spectrometry
biology
intact glycopeptide
hepatocellular carcinoma
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
digestive system diseases
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Hepatocellular carcinoma
embryonic structures
Cancer research
biology.protein
glycoproteome
Alpha-fetoprotein
Subjects
Details
- Language :
- English
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in Oncology
- Accession number :
- edsair.doi.dedup.....f8fe7e3ae68fef58e3c32582f9e80f6a