Amplification of pro-proliferative genes adjacent to the F3 gene in pancreatic adenocarcinoma is associated with worse outcomes.

While the elevated expression of F3 is known to contribute to a hyper-venous thromboembolism (VTE) state in pancreatic adenocarcinoma (PAAD), the basis for elevated F3 expression remains unexplored. This study investigated whether amplification of the genes, ARHGAP29 and SLC44A3, which are adjacent to F3, could explain the amplification of the F3 gene. Thus, precision-guided copy number variation (CNV) analyses were performed using two PAAD data sets: Clinical Proteomic Tumor Analysis Consortium (CPTAC)-PAAD and The Cancer Genome Atlas (TCGA)-PAAD. Kaplan-Meier (KM) analyses demonstrated that patients representing the upper percentiles of CNs for ARHGAP29 and SLC44A3 had significantly worse overall survival (OS) and disease-free survival (DFS) for CPTAC-PAAD. Trends for the same outcomes for OS were observed for TCGA-PAAD. Pearson's correlation tests for ARHGAP29, F3, and SLC44A3 CNs and MSIsensor scores showed statistical significance, indicating that higher amplification was consistent with greater genomic instability. F3 CNs and the F3 CN-based outcome assessments were consistent with the outcomes based on the increased CNs for ARHGAP29 and SLC44A3, for both CPTAC-PAAD and TCGA-PAAD. These findings raise the question of whether a selection for increased CNs of pro-proliferative genes, with a corresponding increase in F3 CNs, contributes to increased VTE and worse outcomes for PAAD?