Pancreatic cancer (PC) is the fourth leading cause of death worldwide. Although the serum carbohydrate antigen (CA)19-9 level is a widely used diagnostic marker of pancreatic cancer, this parameter is not sufficiently sensitive or accurate and cannot be used to screen small, resectable early-stage cancers. Accordingly, screening strategies based on novel serum markers that are more specific and sensitive for pancreatic cancer are urgently needed. Our data showed that CFB, either alone or in combination with CA19-9 (termed ComB-CAN) exhibited good diagnostic ability for early-stage (I-II) pancreatic cancer, with ≥90% sensitivity and 98% specificity. ComB-CAN was much more sensitive than CA 19-9 for discriminating early-stage PC from pancreatitis and pancreatic tumors. To study the potential role of CFB in pancreatic cancer cell (PANC1) carcinogenesis, we used short hairpin (sh) RNAs to generate stable MOCK (shControl) and CFB-knockdown (shCFB) PANC1 cell lines. We also analyzed the transcriptome to identify CFB-related genes. We identified 59 and 86 genes exhibiting a >4-fold increase or decrease, respectively, in CFB-knockdown cells relative to MOCK cells. These genes were subjected to gene ontogeny classification based on an ExDEGA search analysis. RNA-seq data analysis demonstrated the downregulation of proteins involved in cell migration, angiogenesis and ECM in CFB-knockdown cells. These data indicate that an increased CFB level is closely related to pancreatic cancer cell carcinogenesis and supports multiple roles for CFB: oncogenic factor and an early serologic PC diagnostic marker. (This study was supported by grants from the Korean Ministry of Health and Welfare: HI13C2098, and HI16C0257 to Y.-K. Paik)