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

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

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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.

Original languageEnglish
Pages (from-to)5315-5328
Number of pages14
JournalJournal of Proteome Research
Volume20
Issue number12
DOIs
Publication statusPublished - 2021 Dec 3

Bibliographical note

Funding Information:
We are grateful to Dr. Si Young Song at Yonsei University College of Medicine and Dr. Soo Youn Lee at Samsung Medical Center, Sungkyunkwan University, Seoul, Korea for supplying clinical samples for this study. This work was supported by a grant from the Korean Ministry of Health and Welfare (to Y.-K.P., HI16C0257; HI13C2098) and the J.W. Bioscience-Yonsei University Corporative Research Fund (to Y.-K.P., 2021-11-1187).

Publisher Copyright:
© 2021 American Chemical Society.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Chemistry(all)

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