Platform for Personalized Oncology: Integrative analyses reveal novel molecular signatures associated with colorectal cancer relapse.

Approximately 80% of Stage II colon cancer patients are cured by appropriate surgery. However, 20% relapse, and virtually all of these people will die due to metastatic disease. Adjuvant chemotherapy has little or no impact on relapse or survival in Stage II colon cancer, and can only add toxicity without benefit for 80% of the target population that has been cured by surgery. Despite much effort, it is difficult to identify clinical or molecular determinants of outcome in Stage II colon cancer, defeating attempts to target treatments to the 20% of individuals who are destined to relapse. We hypothesized that a multidimensional molecular analysis will identify a combination of factors that serve as prognostic biomarkers in Stage II adenocarcinoma of the colon. The Georgetown informatics team generated and analyzed multi-omics profiling datasets in stage II CRC patients with or without relapse to identify molecular signatures in CRC that may serve both as prognostic markers of recurrence, and also allow for identification of the subgroup of patients who might benefit from adjuvant chemotherapy. The datasets were loaded to GDOC® (Georgetown Database of Cancer) for further mining and analysis. The G-DOC web portal (http://gdoc.georgetown.edu) includes a broad collection of bioinformatics and systems biology tools for analysis and visualization of four major "omics" types: DNA, mRNA, microRNA, and metabolites. Through technology re-use, the G-DOC infrastructure will accelerate progress for a variety of ongoing programs in need of integrative multi-omics analysis, and advance our opportunities to practice effective personalized oncology in the near future.