Abstract B23: Plasma basigin as an early detection biomarker for pancreatic adenocarcinoma

Abstract Poor survival rates for pancreatic adenocarcinoma (PDAC) are in part due to late presentation. Earlier diagnosis is recognized as a means to improve outcomes by increasing the possibility for potentially curative treatment. Identification of early detection biomarkers is a research priority. The stromal compartment is a potential source for biomarkers as a strong desmoplastic response is a hallmark of PDAC. The interaction of mesenchymal, cancer, and inflammatory cells in the tumor induce secretion of autocrine and paracrine effectors and extracellular matrix remodeling enzymes that contribute to tumor growth, invasion, angiogenesis, and metastasis. Basigin (BSG), a cell surface glycoprotein, plays a role in the interaction of cancer and mesenchymal cells through the stimulation of extracellular matrix remodeling enzymes. Circulating BSG has also been demonstrated as a diagnostic/prognostic biomarker for other cancers. We evaluated the potential utility of plasma BSG as a PDAC diagnostic and prognostic biomarker. BSG levels were measured by ELISA in plasma from 106 healthy control subjects (mean = 3.29 ng/ml, 95% CI =3.0 – 3.6), 77 patients with chronic pancreatitis (3.72 ng/ml, 3.3 – 4.1 CI), and 112 pre-treatment samples from patients with PDAC (4.19 ng/ml, 3.9 – 4.5 CI). Nonparametric analysis revealed a significant difference for the model (P = 0.02, Wilcoxon). By ANOVA and Tukey-Kramer post-hoc tests, the distributions of BSG levels in PDAC and healthy control subjects were significantly different (P = 0.0003), but the comparison of PDAC to chronic pancreatitis cases was not significant (P = 0.147). A striking difference was noted after separating the PDAC cases into early stage (I-II) and late stage (III-IV) groups. ANOVA indicated that early stage disease (N = 70, 4.61 ng/ml, 4.2 – 5.0 CI) had significantly elevated BSG levels compared to healthy controls (P &amp;lt; 0.0001), chronic pancreatitis cases (P = 0.006), and late stage PDAC cases (P = 0.003, N = 42, 3.48 ng/ml, 2.9 – 3.9 CI). Increased plasma BSG levels were also significantly related to decreased survival in univariate Cox proportional hazards models (P = 0.01) indicating a 14% increase in risk per 1 ng/ml. This relationship remained significant in multivariate models adjusting for stage and post-diagnosis treatments. The results suggest that circulating BSG is an early stage phenomenon during PDAC development and would apparently be unique in its ability to specifically identify early stage PDAC cases. If validated, this biomarker should substantially contribute to the accuracy of an early detection biomarker panel. Further investigations are warranted into the usefulness of circulating BSG for early detection, selection of patients for surgical resection, identification of recurrence, screening high-risks groups and/or inclusion in panel screens. Citation Format: Samaa Kamal, Matthew A. Firpo, Courtney L. Scaife, Adler G. Douglas, Kenneth M. Boucher, Sean J. Mulvihill. Plasma basigin as an early detection biomarker for pancreatic adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B23.

Topic: Signaling Pathways in Disease
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences