Background: Pancreatic adenocarcinoma is one of the most aggressive and malignant tumor entities; mortality is nearly identical to incidence. Most patients die within a year of diagnosis. Methods: For early and accurate diagnosis and an elucidation of functional aspects, we performed proteome studies by means of a complex antibody microarray with about 1000 binders. We also compared the results to data produced from the very samples at the levels of DNA sequence, promoter methylation, mRNA and microRNA expression as well as genome-wide knock-down analyses. Results: For early diagnosis, several hundred urine and serum samples were studied, yielding diagnostic protein patterns of high accuracy and specificity. Also, variations in the protein abundance and structure in 650 tissue samples were analyzed, using also antibodies that are specific for cancer-associated isoforms. For comparison, 24 pancreatic cancer cell lines and appropriate controls were investigated, examining the cells at steady-state and after induction with various factors such as cytokines. In addition, we measured the resulting variations in the cells’ secretome. Conclusions: The study revealed many new characteristics of the disease including, for example, information about its degree of differentiation, the source of cells and the metastatic potential. The results form a basis for non-invasive and early diagnosis, allow a more accurate grading of the disease and a determination of its metastatic potential. Several therapy-relevant pathways were identified and protein isoforms were revealed that are specific for tumor tissues and have strong relevance to therapy. References: Alhamdani et al. (2010) J. Prot. Res. 9, 963-971. Schröder et al. (2010) Mol. Cell. Prot. 9, 1271-1280. Alhamdani et al. (2010) Proteomics 10, 3203-3207. Sill et al. (2010) BMC Bioinformatics 11, 556. Schmidt et al. (2011) J. Proteome Res. 10, 1316-1322. Mustafa et al. (2011) Mol. Biosyst. 7, 1795-1801. Friedrich et al. (2011) Proteomics 11, 3757-3760. Alhamdani et al. (2012) J. Proteomics 75, 3747-3759. Fredebohm et al. (2012) PLoS ONE 7, e48503.