Identification of a novel serum biomarker for pancreatic cancer, C4b-binding protein α-chain (C4BPA) by quantitative proteomic analysis using tandem mass tags

Kazuyuki Sogawa, Shigetsugu Takano, Fumie Iida, Mamoru Satoh, Sachio Tsuchida, Yusuke Kawashima, Hideyuki Yoshitomi, Akihiro Sanda, Yoshio Kodera, Hirotaka Takizawa, Rintaro Mikata, Masayuki Ohtsuka, Hiroaki Shimizu, Masaru Miyazaki, Osamu Yokosuka, Fumio Nomura

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)


Background: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease due to the lack of specific early diagnostic markers. To improve the outcomes, proteomic approaches are being developed for the discovery of novel biomarkers of PDAC. Methods: Using tandem mass tag labelling and LC-MS/MS, we performed comparative analyses of pre- and postoperative sera from PDAC patients to identify specific serum biomarkers for PDAC. In validation studies, we evaluated the discriminatory power of candidate proteins. Results: Among the 302 proteins analysed, 20 were identified as potential biomarkers, with C4b-binding protein α-chain (C4BPA) and polymeric immunoglobulin receptor (PIGR) being selected for further analysis. The sera levels of C4BPA and PIGR were significantly higher in the preoperative PDAC patients than in the postoperative ones (P<0.008, P<0.036, respectively). In addition, serum C4BPA levels, but not PIGR, in patients with PDAC were significantly higher than those in healthy controls as well as in patients with pancreatitis and other malignancies including biliary tract cancers (BTC) (P<0.001). The respective area under the receiver operator characteristics (ROC) curve (AUC) was 0.860 for C4BPA, 0.846 for CA19-9 and 0.930 for the combination of C4BPA and CA19-9 in PDAC vs non-cancer individuals. The respective AUC was 0.912 for C4BPA, 0.737 for CA19-9 in Stages I and II of PDAC, 0.854 for C4BPA and 0.264 for CA19-9 in PDAC vs BTC. Conclusions: We have demonstrated that C4BPA is a novel serum biomarker for detecting early stage PDAC, as well as for distinguishing PDAC from other gastroenterological cancers. Further analysis in large cohort studies will warrant C4BPA as a promising biomarker of PDAC in clinical use.

Original languageEnglish
Pages (from-to)949-956
Number of pages8
JournalBritish Journal of Cancer
Issue number8
Publication statusPublished - 11 Oct 2016
Externally publishedYes


  • C4BPA
  • PIGR
  • TMT
  • biomarkers
  • early detection
  • pancreatic cancer
  • proteomics
  • serum


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