J Gastrointest Surg DOI 10.1007/s11605-013-2326-y
2013 SSAT PLENARY PRESENTATION
Clinical Significance of Serum COL6A3 in Pancreatic Ductal Adenocarcinoma Christopher Y. Kang & Jonathan Wang & Dierdre Axell-House & Pranay Soni & Mon-Li Chu & Galina Chipitsyna & Konrad Sarosiek & Jocelyn Sendecki & Terry Hyslop & Mazhar Al-Zoubi & Charles J. Yeo & Hwyda A. Arafat
Received: 18 May 2013 / Accepted: 19 August 2013 # 2013 The Society for Surgery of the Alimentary Tract
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 enzymelinked 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. Keywords Pancreatic cancer . Collagen VI . Serum marker . Diagnostic biomarker
Presented as a plenary presentation at the 54th Annual Meeting of the Society for Surgery of the Alimentary Tract, 17–21 May 2013, and an oral presentation at the SSAT Residents and Fellows Research Conference, 17th May 2013, Orlando, FL, USA. C. Y. Kang : J. Wang : D. Axell-House : P. Soni : G. Chipitsyna : K. Sarosiek : M. Al-Zoubi : C. J. Yeo : H. A. Arafat (*) Departments of Surgery and the Jefferson Pancreatic, Biliary &Related Cancer Center, Thomas Jefferson University, 1015 Walnut St, Suite 618 Curtis, Philadelphia, PA 19107, USA e-mail:
[email protected] M.85 %; therefore, the overall 5-year survival rate is only
