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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 |
