Plasma proteome plus site-specific N-glycoprofiling for hepatobiliary carcinomas

Research output: Contribution to journalArticle

Abstract

Hepatobiliary cancer is the third leading cause of cancer death worldwide. Appropriate markers for early diagnosis, monitoring of disease progression, and prediction of postsurgical outcome are still lacking. As the majority of circulating N-glycoproteins are originated from the hepatobiliary system, we sought to explore new markers by assessing the dynamics of N-glycoproteome in plasma samples from patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or combined HCC and CCA (cHCC-CCA). Using a mass spectrometry-based quantitative proteomic approach, we found that 57 of 5358 identified plasma proteins were differentially expressed in hepatobiliary cancers. The levels of four essential proteins, including complement C3 and apolipoprotein C-III in HCC, galectin-3-binding protein in CCA, and 72 kDa inositol polyphosphate 5-phosphatase in cHCC-CCA, were highly correlated with tumor stage, tumor grade, recurrence-free survival, and overall survival. Postproteomic site-specific N-glycan analyses showed that human complement C3 bears high-mannose and hybrid glycoforms rather than complex glycoforms at Asn85. The abundance of complement C3 with mannose-5 or mannose-6 glycoform at Asn85 was associated with HCC tumor grade. Furthermore, stepwise Cox regression analyses revealed that HCC patients with a hybrid glycoform at Asn85 of complement C3 had a lower postsurgery tumor recurrence rate or mortality rate than those with a low amount of complement C3 protein. In conclusion, our data show that particular plasma N-glycoproteins with specific N-glycan compositions could be potential noninvasive markers to evaluate oncological status and prognosis of hepatobiliary cancers.

Original languageEnglish
Pages (from-to)199-212
Number of pages14
JournalJournal of Pathology: Clinical Research
Volume5
Issue number3
DOIs
Publication statusPublished - 2019 Jul 1

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Proteome
Complement C3
Carcinoma
Hepatocellular Carcinoma
Cholangiocarcinoma
Neoplasms
Mannose
Polysaccharides
Glycoproteins
Apolipoprotein C-III
Galectin 3
Recurrence
Survival
Proteomics
Disease Progression
Blood Proteins
Early Diagnosis
Cause of Death
Mass Spectrometry
Carrier Proteins

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

@article{af3111d652a14eb189e3a17bb4d706a3,
title = "Plasma proteome plus site-specific N-glycoprofiling for hepatobiliary carcinomas",
abstract = "Hepatobiliary cancer is the third leading cause of cancer death worldwide. Appropriate markers for early diagnosis, monitoring of disease progression, and prediction of postsurgical outcome are still lacking. As the majority of circulating N-glycoproteins are originated from the hepatobiliary system, we sought to explore new markers by assessing the dynamics of N-glycoproteome in plasma samples from patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), or combined HCC and CCA (cHCC-CCA). Using a mass spectrometry-based quantitative proteomic approach, we found that 57 of 5358 identified plasma proteins were differentially expressed in hepatobiliary cancers. The levels of four essential proteins, including complement C3 and apolipoprotein C-III in HCC, galectin-3-binding protein in CCA, and 72 kDa inositol polyphosphate 5-phosphatase in cHCC-CCA, were highly correlated with tumor stage, tumor grade, recurrence-free survival, and overall survival. Postproteomic site-specific N-glycan analyses showed that human complement C3 bears high-mannose and hybrid glycoforms rather than complex glycoforms at Asn85. The abundance of complement C3 with mannose-5 or mannose-6 glycoform at Asn85 was associated with HCC tumor grade. Furthermore, stepwise Cox regression analyses revealed that HCC patients with a hybrid glycoform at Asn85 of complement C3 had a lower postsurgery tumor recurrence rate or mortality rate than those with a low amount of complement C3 protein. In conclusion, our data show that particular plasma N-glycoproteins with specific N-glycan compositions could be potential noninvasive markers to evaluate oncological status and prognosis of hepatobiliary cancers.",
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Plasma proteome plus site-specific N-glycoprofiling for hepatobiliary carcinomas. / Chang, Ting-Tsung; Cheng, Ji Hong; Tsai, Hung-Wen; Young, Kung-Chia; Hsieh, Sun-Yuan; Ho, Cheng Hsun.

In: Journal of Pathology: Clinical Research, Vol. 5, No. 3, 01.07.2019, p. 199-212.

Research output: Contribution to journalArticle

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T1 - Plasma proteome plus site-specific N-glycoprofiling for hepatobiliary carcinomas

AU - Chang, Ting-Tsung

AU - Cheng, Ji Hong

AU - Tsai, Hung-Wen

AU - Young, Kung-Chia

AU - Hsieh, Sun-Yuan

AU - Ho, Cheng Hsun

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