Identifying key gene sets in metastatic dormancy: ontology enrichment in gene expression profiles from selected human breast cancer patients
Date
2018
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
For approximately 20% of breast cancer patients, many years pass between initial remission and the emergence of distal metastases. These late recurrences are hypothesized to arise from malignant cells shed from the primary tumor that remain dormant in secondary tissues until resuming metastatic proliferation. A central question is the extent to which the dormancy interval is determined by the initial state of cells in the primary tumor, and whether proliferation resumes as the result of changes in the distal microenvironment. Differential gene expression in primary tumors may provide insight into the processes involved in the maintenance of metastatic dormancy. ☐ Four clinical studies providing microarray profiles were identified based on specific endpoints, and follow-up duration. Patient groups were assembled based on disease status and the time to distant metastases. Differential gene expression and ontology enrichment for these patients was evaluated in an automated workflow. ☐ Despite some weakness in differential expression, noteworthy overlap between studies was observed at the level of ontological enrichment. Several biologically relevant terms were detected in enrichments for three or more studies. These included terms such as “platelet degranulation”, “wound healing” and “cell proliferation” all processes that may be are involved in the escape from dormancy.