A global insight into a cancer transcriptional space using pancreatic data: importance, findings and flaws

Abstract

Despite the increasing wealth of available data, the structure of cancer transcriptional space remains largely unknown. Analysis of this space would provide novel insights into the complexity of cancer, assess relative implications in complex biological processes and responses, evaluate the effectiveness of cancer models and help uncover vital facets of cancer biology not apparent from current small-scale studies. We conducted a comprehensive analysis of pancreatic cancer-expression space by integrating data from otherwise disparate studies. We found (i) a clear separation of profiles based on experimental type, with patient tissue samples, cell lines and xenograft models forming distinct groups; (ii) three subgroups within the normal samples adjacent to cancer showing disruptions to biofunctions previously linked to cancer; and (iii) that ectopic subcutaneous xenografts and cell line models do not effectively represent changes occurring in pancreatic cancer. All findings are available from our online resource for independent interrogation. Currently, the most comprehensive analysis of pancreatic cancer to date, our study primarily serves to highlight limitations inherent with a lack of raw data availability, insufficient clinical/histopathological information and ambiguous data processing. It stresses the importance of a global-systems approach to assess and maximise findings from expression profiling of malignant and non-malignant diseases.