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 hepatobilia...
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| Format: | Article |
| Language: | English |
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Wiley
2019-07-01
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| Series: | The Journal of Pathology: Clinical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cjp2.136 |
| _version_ | 1819106087924662272 |
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| author | Ting‐Tsung Chang Ji‐Hong Cheng Hung‐Wen Tsai Kung‐Chia Young Sun‐Yuan Hsieh Cheng‐Hsun Ho |
| author_facet | Ting‐Tsung Chang Ji‐Hong Cheng Hung‐Wen Tsai Kung‐Chia Young Sun‐Yuan Hsieh Cheng‐Hsun Ho |
| author_sort | Ting‐Tsung Chang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T02:32:34Z |
| format | Article |
| id | doaj.art-97d6fbeca62b4d46b2cd6811bdb685ab |
| institution | Directory Open Access Journal |
| issn | 2056-4538 |
| language | English |
| last_indexed | 2024-12-22T02:32:34Z |
| publishDate | 2019-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Journal of Pathology: Clinical Research |
| spelling | doaj.art-97d6fbeca62b4d46b2cd6811bdb685ab2022-12-21T18:41:52ZengWileyThe Journal of Pathology: Clinical Research2056-45382019-07-015319921210.1002/cjp2.136Plasma proteome plus site‐specific N‐glycoprofiling for hepatobiliary carcinomasTing‐Tsung Chang0Ji‐Hong Cheng1Hung‐Wen Tsai2Kung‐Chia Young3Sun‐Yuan Hsieh4Cheng‐Hsun Ho5Department of Internal Medicine National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan TaiwanDepartment of Computer Science and Information Engineering College of Electrical Engineering and Computer Science, National Cheng Kung University Tainan TaiwanDepartment of Pathology National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan TaiwanDepartment of Medical Laboratory Science and Biotechnology College of Medicine, National Cheng Kung University Tainan TaiwanDepartment of Computer Science and Information Engineering College of Electrical Engineering and Computer Science, National Cheng Kung University Tainan TaiwanDepartment of Medical Laboratory Science College of Medicine, I‐Shou University Kaohsiung City TaiwanAbstract 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.https://doi.org/10.1002/cjp2.136hepatocellular carcinomacholangiocarcinomaproteomicglycosylationmass spectrometry |
| spellingShingle | Ting‐Tsung Chang Ji‐Hong Cheng Hung‐Wen Tsai Kung‐Chia Young Sun‐Yuan Hsieh Cheng‐Hsun Ho Plasma proteome plus site‐specific N‐glycoprofiling for hepatobiliary carcinomas The Journal of Pathology: Clinical Research hepatocellular carcinoma cholangiocarcinoma proteomic glycosylation mass spectrometry |
| title | Plasma proteome plus site‐specific N‐glycoprofiling for hepatobiliary carcinomas |
| title_full | Plasma proteome plus site‐specific N‐glycoprofiling for hepatobiliary carcinomas |
| title_fullStr | Plasma proteome plus site‐specific N‐glycoprofiling for hepatobiliary carcinomas |
| title_full_unstemmed | Plasma proteome plus site‐specific N‐glycoprofiling for hepatobiliary carcinomas |
| title_short | Plasma proteome plus site‐specific N‐glycoprofiling for hepatobiliary carcinomas |
| title_sort | plasma proteome plus site specific n glycoprofiling for hepatobiliary carcinomas |
| topic | hepatocellular carcinoma cholangiocarcinoma proteomic glycosylation mass spectrometry |
| url | https://doi.org/10.1002/cjp2.136 |
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