title: Identification of human complement factor B as a novel biomarker candidate for pancreatic ductal adenocarcinoma.
abstract: Pancreatic cancer (PC; pancreatic ductal adenocarcinoma) is characterized by significant morbidity and mortality worldwide. Although carbohydrate antigen (CA) 19-9 has been known as a PC biomarker, it is not commonly used for general screening because of its low sensitivity and specificity. Therefore, there is an urgent need to develop a new biomarker for PC diagnosis in the earlier stage of cancer. To search for a novel serologic PC biomarker, we carried out an integrated proteomic analysis for a total of 185 pooled or individual plasma from healthy donors and patients with five disease groups including chronic pancreatitis (CP), PC, and other cancers (e.g., hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer) and identified complement factor b (CFB) as a candidate serologic biomarker for PC diagnosis. Immunoblot analysis of CFB revealed more than two times higher expression in plasma samples from PC patients compared with plasma from individuals without PC. Immunoprecipitation coupled to mass spectrometry analysis confirmed both molecular identity and higher expression of CFB in PC samples. CFB showed distinctly higher specificity than CA 19-9 for PC against other types of digestive cancers and in discriminating PC patients from non-PC patients (p < 0.0001). In receiver operator characteristic curve analysis, CFB showed an area under curve of 0.958 (95% CI: 0.956 to 0.959) compared with 0.833 (95% CI: 0.829 to 0.837) for CA 19-9. Furthermore, the Y-index of CFB was much higher than that of CA 19-9 (71.0 vs 50.4), suggesting that CFB outperforms CA 19-9 in discriminating PC from CP and other gastrointestinal cancers. This was further supported by immunoprecipitation and qRT-PCR assays showing higher expression of CFB in PC cell lines than in normal cell lines. A combination of CFB and CA 19-9 showed markedly improved sensitivity (90.1 vs 73.1%) over that of CFB alone in the diagnosis of PC against non-PC, with similar specificity (97.2 vs 97.9%). Thus, our results identify CFB as a novel serologic PC biomarker candidate and warrant further investigation into a large-scale validation and its role in molecular mechanism of pancreatic carcinogenesis.
authors: Yonsei Proteome Research Center and ‡Department of Integrated OMICS for Biomedical Science and Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University , 50 Yonsei-ro, Sudaemoon-ku, Seoul 120-749, Korea.
authors: Min Jung
authors: MJ
authors: Lee
authors: Keun
authors: K
authors: Na
authors: Seul-Ki
authors: SK
authors: Jeong
authors: Jong-Sun
authors: JS
authors: Lim
authors: Sun A
authors: SA
authors: Kim
authors: Min-Ji
authors: MJ
authors: Lee
authors: Si Young
authors: SY
authors: Song
authors: Hoguen
authors: H
authors: Kim
authors: William S
authors: WS
authors: Hancock
authors: Young-Ki
authors: YK
authors: Paik
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis*; D045744:Cell Line, Tumor; D011415:Complement Factor B / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007091:Image Processing, Computer-Assisted; D047468:Immunoprecipitation; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D040901:Proteomics / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D053719:Tandem Mass Spectrometry; D014357:Trypsin
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D014357:Trypsin; D011415:Complement Factor B
keywords: biomarker; carbohydrate antigen 19-9; complement factor b; pancreatic cancers