Abstract A3: Validation of candidate serum biomarkers demonstrates the potential of CUZD1 and LAMC2 to complement CA19.9 for pancreatic cancer diagnosis.

Pancreatic cancer is a significant cause of cancer mortality. The high mortality rate of this disease is associated with the complete lack of early clinical symptoms. Moreover, existing tumor markers (e.g., CA19-9) are not sufficiently sensitive and/or specific to early differentiate benign from cancer patients, therefore there is an urgent need for improved serum markers that can improve both early diagnosis and therapeutic monitoring. In pursuit of novel candidate markers, several genomic, transcriptomic, and proteomic studies have been recently reported, however no specific tumor marker has been as yet identified that can outperform CA19-9. In an effort to capture the complex pathophysiology of this disease we employed an integrated biomarker discovery approach which combines: 1) in vitro cell line secretome analyses, 2) ex vivo proteomic analysis of pancreatic ascites and pancreatic juice; 3) quantitative pancreatic tissue proteomics; 4) in silico mining of tissue expression databases and 5) extensive microarray data mining. A systemic grading system was applied to our lists of identified markers and the top-ranked candidates were selected for further validation in larger cohorts. Herein, we present our first-step validation of the two most promising candidates, CUB and zona pellucida-like domain-containing protein 1 (CUZD1) and laminin subunit gamma-2 (LAMC2), using commercially available enzyme-linked immunosorbent assays (ELISAs) in 150 serum samples including: 50 pancreatic ductal adenocarcinoma patients (PDAC), 50 patients with benign diseases and 50 healthy individuals. Statistical analysis indicated that CUZD1 and LAMC2 were significantly elevated in PDAC versus healthy controls and also significantly increased in PDAC versus benign diseases (p<0.0001). Individually, LAMC2 had similar efficacy and CUZD-1 slightly outperformed CA19-9 (AUCs: 0.84 for CA19.9, 0.864 for CUZD1 and 0.785 for LAMC2). Importantly, significant complementarity was observed between CUZD1 and CA19.9 (combined AUC: 0.942) with an overall sensitivity of 88% and specificity of 94% in benign versus PDAC cases. Our initial results indicate that both CUZD1 and LAMC2 have the potential to complement CA19.9. More validation studies in larger sample sets with more defined clinical annotations (e.g., stage, clinical outcomes) are ongoing in order to explore further the possibility of combining CUZD1 and LAMC2 to improve the diagnostic performance of CA19.9. Citation Format: Caitlin Chrystoja, Hari Kosanam, Ioannis Prassas, Alison Chan, Apostolos Dimitromanolakis, Shalini Makawita, Antoninus Soosaipillai, Ivan Blasutig, Eleftherios P. Diamandis. Validation of candidate serum biomarkers demonstrates the potential of CUZD1 and LAMC2 to complement CA19.9 for pancreatic cancer diagnosis. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A3.