PXD047043 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Inhibition of Alternative Complement Pathway May Cause Secretion of Factor B, Enabling an Early Detection of Pancreatic Cancer |
Description | This study aims to elucidate the cellular mechanisms underlying the secretion of factor B (CFB), recognized for its dual role as an early biomarker of pancreatic ductal adenocarcinoma (PDAC) and as the initiating substrate for the alternative complement pathway (ACP), a crucial component of the innate immune system. Employing parallel reaction monitoring analysis, we substantiated CFB's consistent ~2-fold elevated expression in PDAC patients compared to both healthy donors (HD) and chronic pancreatitis (CP) patients, thereby affirming its status as a cancer biomarker, as previously established through ELISA methods. In contrast to CFB expression, we observed heightened ACP activity in the patients of CP and other benign cancer compared to both HD and PDAC patients, prompting further exploration of a potential functional link between ACP and PDAC. To investigate the cellular secretion mechanism of CFB, we conducted protein-protein interaction analyses involving key complement proteins and their regulatory factors within the ACP cascade. These analyses encompassed blood samples from PDAC patients spanning various disease stages, alongside cancer cell lines. Our findings unveiled an intricate control system governing the ACP and its regulatory factors, including KRAS mutation, adrenomedullin (AM), and factor H (CFH). Notably, AM emerged as a pivotal player in CFB secretion, activating CFH and thereby promoting its predominant binding to C3b over CFB. Mechanistically, our data propose that KRAS mutation stimulates AM expression, subsequently enhancing CFH activity in the fluid phase through binding. This heightened AM-CFH interaction evidently conferred a greater affinity for C3b over CFB, potentially leading to suppression of the ACP cascade. This sequence of events likely culminated in the release of ductal CFB into plasma during the early stages of PDAC. Thus, our findings illuminate an intriguing trade-off between suppressed ACP activity and the early detection of PDAC. |
HostingRepository | PRIDE |
AnnounceDate | 2024-05-21 |
AnnouncementXML | Submission_2024-05-21_12:13:19.506.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jin-Young Cho |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-11-17 12:26:09 | ID requested | |
⏵ 1 | 2024-05-21 12:13:20 | announced | |
Publication List
Lee MJ, Cho JY, Bae S, Jung HS, Kang CM, Kim SH, Choi HJ, Lee CK, Kim H, Jo D, Paik YK, Inhibition of the Alternative Complement Pathway May Cause Secretion of Factor B, Enabling an Early Detection of Pancreatic Cancer. J Proteome Res, 23(3):985-998(2024) [pubmed] |
10.1021/acs.jproteome.3c00695; |
Keyword List
submitter keyword: complement factor B, proteomics,adrenomedullin, alternative pathway, pancreatic ductal adenocarcinoma, cancer biomarker, complement factor H |
Contact List
Young-Ki Paik |
contact affiliation | Yonsei Proteome Research Center, Yonsei University |
contact email | paikyk@gmail.com |
lab head | |
Jin-Young Cho |
contact affiliation | Yonsei Proteome Research Center |
contact email | chojy@proteomix.org |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047043
- Label: PRIDE project
- Name: Inhibition of Alternative Complement Pathway May Cause Secretion of Factor B, Enabling an Early Detection of Pancreatic Cancer