In the current study, researchers scanned the activity of thousands of genes in high grade serous ovarian cancers from 129 patients with an advanced stage of the disease. They then sifted the data using an algorithm called rISIS, which randomly assigns the tumor samples to different groups until it finds a grouping with a distinct set of genetic characteristics. That grouping represents a potential cancer subtype.
The technique yielded four possible subtypes of high grade serous ovarian cancer, but only one of them held up when researchers applied a different technique for scanning gene activity. When researchers catalogued the genes that were particularly active -- or "highly expressed" -- in that single subtype, a key trend appeared: many of the genes were known to be involved in angiogenesis, the process by which tumors build blood vessels to tap into the bloodstream for oxygen and nutrients. This distinctive array of overactive genes was dubbed the "angiogenesis signature."
A common shortcoming of gene-profiling studies is that the results often aren't reproducible: different labs obtain different gene signatures for the same types of cancer. To ensure their findings were not skewed by their lab procedures or testing methods, the Dana-Farber investigators analyzed data from ten published, independent studies of gene expression in serous ovarian cancer. Together, these studies involved 1,606 ovarian cancer patients.
"The analysis confirmed our finding," Quackenbush relates. "The angiogenic [blood vessel-producing] subtype is real." When investigators analyzed the medical records of those 1,606 patients, they found that those with the angiogenic subtype tended to have more advanced, aggressive tumors than those without the subtype.
A clinical trial will be ne
|Contact: Bill Schaller|
Dana-Farber Cancer Institute