Proteomics

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Intact N-glycopeptides and proteomics from HCC tissue tumors with low and high AFP concentrations


ABSTRACT: Hepatocellular carcinoma (HCC) is still one of the malignant tumors with high morbidity and mortality in China and worldwide. Although AFP have been widely used as important biomarkers for HCC diagnosis and evaluation, the AFP level has a huge variation among HCC patient populations. 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. Here, an integrated glycoproteomic and proteomic analysis of low and high AFP level of HCC tumors was performed to investigate the intrinsic heterogeneities of site-specific glycosylation associated with different AFP levels of HCC. we identified many commonly altered site-specific 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 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 high-regulated 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

SUBMITTER: Ting Zhao  

LAB HEAD: Sun Lab

PROVIDER: PXD016406 | Pride | 2020-03-19

REPOSITORIES: Pride

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Publications

Heterogeneities of Site-Specific <i>N</i>-Glycosylation in HCC Tumors With Low and High AFP Concentrations.

Zhao Ting T   Jia Li L   Li Jun J   Ma Chen C   Wu Jingyu J   Shen Jiechen J   Dang Liuyi L   Zhu Bojing B   Li Pengfei P   Zhi Yuan Y   Lan Rongxia R   Xu Yintai Y   Hao Zhifang Z   Chai Yichao Y   Li Qingshan Q   Hu Liangshuo L   Sun Shisheng S  

Frontiers in oncology 20200421


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 intrins  ...[more]

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