title: Clinical significance of serum COL6A3 in pancreatic ductal adenocarcinoma.
abstract: Type VI collagen (COL6) forms a microfibrillar network often associated with type I collagen and constitutes a major component of the desmoplastic reaction in pancreatic ductal adenocarcinoma (PDA). We have demonstrated recently that the α3 chain of COL6, COL6A3, is highly expressed in PDA tissue and undergoes tumor-specific alternative splicing. In this study, we investigated the diagnostic value and clinical significance of circulating COL6A3 protein and mRNA in PDA. COL6A3 levels in sera from patients with PDA (n = 44), benign lesions (n = 46) and age-matched healthy volunteers (n = 30) were analyzed by enzyme-linked immunosorbent assays (ELISA). Predictive abilities of COL6A3 were examined using receiver operating characteristic (ROC) curves from logistic regression models for PDA versus normal or benign serum levels. Expression levels were correlated with clinicopathological parameters. Real-time PCR was used to analyze the presence of COL6A3 mRNA containing alternative spliced exons E3, E4, and E6. Circulating COL6A3 protein levels were significantly elevated in PDA patients when compared to healthy sera (p = 0.0001) and benign lesions (p = 0.0035). The overall area under the ROC was 0.975. Log(COL6A3) alone provided good discrimination between PDA and benign lesions (area under the curve (AUC) = 0.817), but combined with CA19-9 provided excellent discrimination (AUC = 0.904). Interestingly, high COL6A3 serum levels were significantly associated with perineural invasion and cigarette smoking. Combined E3, E4, and E6 serum RNA values provided good sensitivity but low specificity. Our data demonstrate for the first time the potential clinical significance of circulating COL6A3 in the diagnosis of pancreatic malignancy.
authors.affiliation: Departments of Surgery and the Jefferson Pancreatic, Biliary &Related Cancer Center, Thomas Jefferson University, 1015 Walnut St, Suite 618 Curtis, Philadelphia, PA, 19107, USA.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Kang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wang
authors.forename: Dierdre
authors.initials: D
authors.lastname: Axell-House
authors.forename: Pranay
authors.initials: P
authors.lastname: Soni
authors.forename: Mon-Li
authors.initials: ML
authors.lastname: Chu
authors.forename: Galina
authors.initials: G
authors.lastname: Chipitsyna
authors.forename: Konrad
authors.initials: K
authors.lastname: Sarosiek
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Sendecki
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: Mazhar
authors.initials: M
authors.lastname: Al-Zoubi
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Hwyda A
authors.initials: HA
authors.lastname: Arafat
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000473:pathology; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood; D016022:Case-Control Studies; D024142:Collagen Type VI / Q000097:blood* / Q000235:genetics; D017615:Enteric Nervous System / Q000473:pathology; D005091:Exons; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010179:Pancreas / Q000294:innervation; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000097:blood*; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D024142:Collagen Type VI; D012333:RNA, Messenger