Their study, “A Systems Biology Approach to Understanding the Pathophysiology of High-Grade Serous Ovarian Cancer: Focus on Iron and Fatty Acid Metabolism,” was published in OMICS: A Journal Of Integrative Biology.
High-grade serous ovarian cancer (HGSOC) is the most common and aggressive type of ovarian cancer, with only 35 percent of patients living past the five-year mark.
Like many cancer types, ovarian cancer cells are known to retain iron more extensively than normal cells. Iron is needed for DNA replication and participates in multiple cancer signaling pathways. But the exact role of iron in ovarian cancer remains unclear.
Researchers believe that understanding the molecular basis of cancer progression and the role iron plays in the disease may open up better therapeutic opportunities.
UConn Health researchers examined four publicly available gene expression datasets, comparing different cell types. The idea was to find common expression patterns that could shed light on iron’s role in ovarian cancer’s development and progression.
Of the four datasets, two used cells from HGSOC and their environment. The third used fallopian and HGSOC cells, but because of the similarity in their gene expression profiles, researchers combined the information as HGSOC dataset. In the fourth dataset, researchers used HGSOC stem cells.
“Since each dataset represents a different aspect of HGSOC, an overlap in results between the different datasets may be considered a measure of their robustness,” the investigators said, supporting their choice of the datasets analyzed.
Comparing the gene expression profiles, researchers found that all four datasets showed an increase in three pathways that encourage fatty acid import, metabolism, and regulation.
Iron-related genes were particularly affected, providing a possible explanation for the higher fatty acid levels in iron-rich ovarian cancer cells.
“Iron may be playing a critical role in increased fatty acid synthesis in cancer. No one knew that before,” Anna Konstorum, PhD, postdoctoral fellow at UConn Health and the first author of the paper, said in a press release.
Fatty acids are the building blocks of fats, or lipids, for body tissues and play a key role in immunity, inflammation, and cell-to-cell signaling. Previous studies have indicated a role for fats in ovarian cancer.
“When you read about cancer, it’s almost always about genetics. But it’s only recently that people have begun to think about metabolism; what cells do, instead of how they’re made,” said Reinhard Laubenbacher, professor at UConn Health.
The experimental validations of the links identified in this study are underway.
“We aim to stimulate inquiry into the interdependence between iron and [fatty acid] metabolism in HGSOC and other cancers. This will enhance not only understanding of the basic biology of HGSOC but also potentially identify vulnerabilities that can be exploited therapeutically,” the investigators concluded.
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