PXD047043-1

PXD047043 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-17 12:26:09	ID requested
⏵ 1	2024-05-21 12:13:20	announced

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;

submitter keyword: complement factor B, proteomics,adrenomedullin, alternative pathway, pancreatic ductal adenocarcinoma, cancer biomarker, complement factor H

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD047043

PRIDE project URI

• PRIDE
  1. PXD047043
     1. Label: PRIDE project
     2. Name: Inhibition of Alternative Complement Pathway May Cause Secretion of Factor B, Enabling an Early Detection of Pancreatic Cancer