To discover pathways potentially contributing to the metastatic process, we looked for genes upregulated in the PDAC versus control experiments (‘Good’ versus control and ‘Bad’ versus control) and in the Metastases versus PDAC comparison. In total 29 genes met these criteria, including β-catenin, ANP32A, HPGD, SET and SP1 (fold change between

metastases versus PDAC respectively 3.0, 3.4, 2.5, 3.6 and 2.0; all p < 0.001) ( Additional file 1: Table S1). Table 4 Upregulated KEGG pathways (GENECODIS) in primary PDAC and metastatic PDAC samples   PDACversusMetastases MetastasesversusPDAC KEGG Pathwaya P-value Upregulated genesb P-value Upregulated genesb Wnt signalling 0.00969 FZD1, FZD10, WNT5A, CCND2     TGFβ pathway 0.00574 LTBP1, THBS4, MBPR1B 0.00100 SP1, PPP2R1B, ACVR1C learn more a KEGG analysis was performed on respectively 278 and 80 genes Bromosporine in vitro upregulated in the PDAC and metastases samples using GENECODIS. b A selection of upregulated genes contributing to the pathways, is given. Discussion Unravelling the molecular

characteristics of pancreatic cancer is crucial for a better understanding of the tumour biology in order to develop novel therapeutic strategies. Correlation of gene expression profiles with patient survival might detect genes and pathways that drive PDAC invasiveness as clinicopathological parameters alone seem not sufficient to explain the variability in survival after curative resection. Therefore, in the present study, we performed whole genome expression analysis of Rucaparib chemical structure 2 subgroups of patients with extremely diverging overall and disease-free survival rates, despite having similar clinicopathological features. In contrast to previous studies that used

microdissection or fine needle aspiration techniques to enrich the samples for neoplastic cells [11, 19, 20], we used whole-tumour samples with the aim not to exclude the tumour micro-environment even though discrimination between tumoural and environmental RNA is technically impossible in whole-tumour samples. On the other hand, PDAC is characterized by an abundant desmoplastic stromal reaction, which plays an important role in tumorigenesis, tumour progression, and therapy resistance [12, 13]. Indeed, increasingly new therapeutic regimens are studying agents that aim to target the desmoplastic stromal reaction [21–23]. Therefore, in order to keep the AG-120 nmr molecular information of the microenvironment but to reduce background RNA contamination, we used high-quality snap-frozen samples with a pathologically proven minimum of 30% cancer cells. This approach led to a small but still representative sample size for microarray analysis. In our study, the Integrin and Ephrin pathways were upregulated in all PDAC samples, irrespective of outcome. These pathways were not highlighted in studies on microdissected PDAC [11].