title: Serum α1β-glycoprotein and afamin ratio as potential diagnostic and prognostic markers in cholangiocarcinoma.
abstract: Cholangiocarcinoma (CCA) affects the intra- and extrahepatic bile ducts and is commonly burdened by a late presentation and resulting high mortality rate. Accordingly, finding non-invasive biomarkers with adequate diagnostic/prognostic values is a priority in high-risk populations. In this study, we analyzed proteomes of serum samples from six CCA cases and ten healthy subjects using two-dimensional polyacrylamide gel electrophoresis to identify CCA-associated spots. Thirty-six CCA-associated proteins found in sera were identified by mass spectrometry. α1β-Glycoprotein (A1BG) and afamin (AFM) were detected consistently at different degrees in CCA sera compared with controls and were validated for their diagnostic and prognostic potential in a larger cohort of 64 patients with CCA, 4 with benign biliary diseases and 20 healthy subjects and compared between pre- and postsurgery serum samples from 26 CCA patients to ascertain a prognostic correlation. A single blot test developed to assess the serum A1BG/AFM ratio could detect CCA cases with 87.5% specificity, 84.4% sensitivity and the levels were significantly higher in CCA compared with controls. A high level of postoperative serum A1BG/AFM ratio was associated with worse outcomes and the infiltration of resection margins. The A1BG/AFM ratio may constitute a novel non-invasive candidate marker to diagnose CCA and its outcomes with high specificity and sensitivity. Prospective studies are awaited to demonstrate the clinical value of this observation.
authors.affiliation: Department of Biochemistry, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Arthit
authors.initials: A
authors.lastname: Tolek
authors.forename: Chaisiri
authors.initials: C
authors.lastname: Wongkham
authors.forename: Siriporn
authors.initials: S
authors.lastname: Proungvitaya
authors.forename: Atit
authors.initials: A
authors.lastname: Silsirivanit
authors.forename: Sittiruk
authors.initials: S
authors.lastname: Roytrakul
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000097:blood / Q000175:diagnosis*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D018281:Cholangiocarcinoma / Q000097:blood / Q000175:diagnosis*; D015331:Cohort Studies; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin; D000075462:Serum Albumin, Human
chemical_list: C048566:A1BG protein, human; C088246:AFM protein, human; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D012709:Serum Albumin; D000075462:Serum Albumin, Human