Gene expression profiling has been applied to predict metastatic recurrence, the leading cause of deaths in patients with colorectal carcinoma. However, the biological mechanism is not completely understood, driving poor clinical outcomes.
To address this issue, Dan Beauchamp, M.D., Bing Zhang, Ph.D., and colleagues analyzed the 11 human microarray datasets from 1,295 tumor specimens as well as gene expression data from mouse models. Cells with invasiveness and metastatic capability expressed higher levels of a nuclear factor of activated T cell (NFAT), a family of transcription factors that govern functions as diverse as cell proliferation, survival and invasion.
An elevated expression level of NFATc1, a member of the NFAT family, is associated with increased colon cancer cell invasion and metastasis and poor prognosis in stage II and stage III colorectal cancer patients.
Thus, the NFATc1-driven transcriptional program represents a novel, biologically anchored gene expression signature for identifying colon cancers with high risk of metastatic recurrence, the researchers conclude in the December 1 issue of Cancer Research.
This research was supported by National Institutes of Health grants GM088822, CA095103, CA158472, and CA9060625.
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