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Early Diagnostic Ability of Human Complement Factor B in Pancreatic Cancer Is Partly Linked to Its Potential Tumor-Promoting Role

Authors
 Min Jung Lee  ;  Keun Na  ;  Heon Shin  ;  Chae-Yeon Kim  ;  Jin-Young Cho  ;  Chang Moo Kang  ;  Sung Hyun Kim  ;  Hoguen Kim  ;  Hye Jin Choi  ;  Choong-Kun Lee  ;  Sumi Bae  ;  Sunghwa Son  ;  Young-Ki Paik 
Citation
 JOURNAL OF PROTEOME RESEARCH, Vol.20(12) : 5315-5328, 2021-12 
Journal Title
JOURNAL OF PROTEOME RESEARCH
ISSN
 1535-3893 
Issue Date
2021-12
Keywords
CA-19-9 ; ComB-CAN ; PDAC ; complement factor B ; early detection ; pancreatic cancer ; tumor promotion
Abstract
Although plasma complement factor B (CFB, NX_P00751), both alone and in combination with CA19-9 (i.e., the ComB-CAN), previously exhibited a reliable diagnostic ability for pancreatic cancer (PC), its detectability of the early stages and the cancer detection mechanism remained elusive. We first evaluated the diagnostic accuracy of ComB-CAN using plasma samples from healthy donors (HDs), patients with chronic pancreatitis (CP), and patients with different PC stages (I/II vs III/IV). An analysis of the area under the curve (AUC) by PanelComposer using logistic regression revealed that ComB-CAN has a superior diagnostic ability for early-stage PC (97.1.% [95% confidence interval (CI): (97.1-97.2)]) compared with CFB (94.3% [95% CI: 94.2-94.4]) or CA19-9 alone (34.3% [95% CI: 34.1-34.4]). In the comparisons of all stages of patients with PC vs CP and HDs, the AUC values of ComB-CAN, CFB, and CA19-9 were 0.983 (95% CI: 0.983-0.983), 0.950 (95% CI: 0.950-0.951), and 0.873 (95% CI: 0.873-0.874), respectively. We then investigated the molecular mechanism underlying the detection of early-stage PC by using stable cell lines of CFB knockdown and CFB overexpression. A global transcriptomic analysis coupled to cell invasion assays of both CFB-modulated cell lines suggested that CFB plays a tumor-promoting role in PC, which likely initiates the PI3K-AKT cancer signaling pathway. Thus our study establishes ComB-CAN as a reliable early diagnostic marker for PC that can be clinically applied for early PC screening in the general public.
Full Text
https://pubs.acs.org/doi/10.1021/acs.jproteome.1c00805
DOI
10.1021/acs.jproteome.1c00805
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Chang Moo(강창무) ORCID logo https://orcid.org/0000-0002-5382-4658
Kim, Sung Hyun(김성현) ORCID logo https://orcid.org/0000-0001-7683-9687
Kim, Hogeun(김호근)
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Choi, Hye Jin(최혜진) ORCID logo https://orcid.org/0000-0001-5917-1400
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187324
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