New insight into ovarian cancer progression could prevent metastasis

By Robyn Boyle, RPh, for MDLinx | December 13, 2017

Research published in Nature Communications has shed light on the biological processes and mechanisms involved in ovarian cancer. The information could lead to targeted therapy to prevent progression of the disease.

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Ovarian cancer accounts for more deaths than any other cancer of the female reproductive system.

Ovarian cancer accounts for more deaths than any other cancer of the female reproductive system. In approximately 80% of women, the disease is diagnosed after it has already metastasized; in addition, many women become resistant to treatment. These factors are primarily responsible for the high mortality rate.

The ability of ovarian cancer cells to aggressively invade and metastasize is enhanced through epithelial-to-mesenchymal transition (EMT). This process is associated with loss of cell adhesion proteins and increased invasion, migration, and cell proliferation. Recent studies have suggested that long non-coding RNA (lncRNA) can modulate gene expression and play a role in EMT in various cancers, although the role in regulating EMT in ovarian cancer is not understood.

In this study, an investigative team led by Ramkrishna Mitra from the Sidney Kimmel Cancer Center’s Department of Cancer Biology at Thomas Jefferson University in Philadelphia, PA, hoped to unravel the mechanism of EMT. They systematically identified a number of lncRNA that are overexpressed in ovarian cancer and evaluated their role in EMT.

Researchers assessed more than 700 ovarian cancer molecule profiles, including genomic data sets of 320 women with ovarian cancer from four patient cohorts. The integrated analysis revealed reproducible regulation of EMT by lncRNA in ovarian cancer.

“This study increases understanding of lncRNA-mediated regulatory mechanism of ovarian cancer EMT and increases knowledge of the processes involved in ovarian cancer metastasis that may be targetable,” the authors wrote.

They also found that increased expression of DNM30S, a specific lncRNA, was significantly correlated with reduced overall survival in ovarian cancer in three of four patient cohorts, which could potentially offer a tool for prognosis.

Finally, to determine the functional significance of altered DNM30S levels in EMT, the research team evaluated the effects on lncRNA after reduced expression of DNM30S. They found that multiple EMT-linked pathways were affected. Based on these observations, they suggested that targeting lncRNA might be a treatment strategy for ovarian cancer.

“Taken together, our comprehensive analysis provides essential insights into ovarian cancer EMT and reveal(s) the critical lncRNA and specifically, DNM3OS that regulate it. Our results open new avenues for targeting EMT in ovarian cancer,” the researchers concluded.

The investigators plan to continue to clarify the mechanism of metastasis and potentially translate the information into clinical applications to reduce progression of ovarian cancer.

To read more about this study, click here

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