TY - JOUR
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
N1 - Funding Information:
We thank Human Biobank, Research Center of Clinical Medicine of National Cheng Kung University Hospital, and Dr. Pin-Nan Cheng from the Department of Internal Medicine of National Cheng Kung University Hospital, for providing samples and clinical data from the patients with hepatobiliary cancers and the control subjects, respectively. We also thank Mithra Biotechnology Incorporation for the liquid chromatography–tandem mass spectrometry analyses. We thank Dr. Yi-Hsuan Ho (Division of Biological Sciences, University of California – San Diego, CA, USA) for proofreading the article. This work was supported by grants 103-2321-B-006-033, 104-2321-B-006-014, 105-2321-B-006-006, 106-2314-B-006-071-MY2, and 107-2314-B-214-009 from the Ministry of Science and Technology, Taiwan and by the grant NCKUH-10509007 from National Cheng Kung University Hospital.
Funding Information:
We thank Human Biobank, Research Center of Clinical Medicine of National Cheng Kung University Hospital, and Dr. Pin-Nan Cheng from the Department of Internal Medicine of National Cheng Kung University Hospital, for providing samples and clinical data from the patients with hepatobiliary cancers and the control subjects, respectively. We also thank Mithra Biotechnology Incorporation for the liquid chromatography?tandem mass spectrometry analyses. We thank Dr. Yi-Hsuan Ho (Division of Biological Sciences, University of California ? San Diego, CA, USA) for proofreading the article. This work was supported by grants 103-2321-B-006-033, 104-2321-B-006-014, 105-2321-B-006-006, 106-2314-B-006-071-MY2, and 107-2314-B-214-009 from the Ministry of Science and Technology, Taiwan and by the grant NCKUH-10509007 from National Cheng Kung University Hospital.
Publisher Copyright:
© 2019 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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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U2 - 10.1002/cjp2.136
DO - 10.1002/cjp2.136
M3 - Article
C2 - 31136099
AN - SCOPUS:85068089540
VL - 5
SP - 199
EP - 212
JO - Journal of Pathology: Clinical Research
JF - Journal of Pathology: Clinical Research
SN - 2056-4538
IS - 3
ER -