Researchers from Western CT Health Network Biomedical Research Institute Discover Long-Dormant Viruses Could Later Affect Cancer Outcomes

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Sequencing Results disclose viral products inside ovarian cancer tissues.

“This research is opening a new door. To date, viral microRNAs were not considered in cancer patients,” Dr. Cristiano Ferlini said. “We can use the fact that there are some viral components inside cells to help personalize cancer treatments.”

Researchers from the Western Connecticut Health Network (WCHN) Biomedical Research Institute have discovered that a virus contracted early in life can lay dormant in human cells and be reactivated years later when cancer is diagnosed, possibly changing the outcomes of the disease.

Cristiano Ferlini, MD, the Research Institute’s Rudy and Sally Ruggles Endowed Chief of Cancer Research, and his colleagues made this discovery by investigating viral microRNA expression in a series of ovarian cancer tissue samples taken from The Cancer Genome Atlas database. They found that viral microRNAs were more frequently expressed in ovarian cancer tissue than in normal tissue, and that two microRNAs significantly predicted outcome in the disease.

MicroRNAs, which regulate the expression of genes and are involved in all aspects of a cell’s life, are known to be expressed in cancers. However, when a virus infects a human cell, that virus can “hijack” the behavior of a cell through the expression of viral microRNAs.

“A herpes virus can stay inside a cell forever. Once the virus gets inside the DNA of the cell, it can stay silent for a number of years until the virus is reactivated,” Dr. Ferlini explained. “For example, many people have the herpes simplex virus that produces cold sores. This virus can be reactivated when someone is exposed to a cold.”

According to Dr. Ferlini, The Cancer Genome Atlas (TCGA) microRNA mapping conducted to date only mapped for human microRNAs and not viral microRNAs. Therefore, the researchers downloaded the raw data from 487 patients with serous ovarian cancer from TCGA and mapped it for viral microRNAs, cross validating their finding with a second group of ovarian cancer samples. The results of the study were published in PLoS One.

They found that viral microRNAs were expressed in ovarian cancer tissues. In addition, they compared the frequency of viral microRNA expression and found that it was more frequently expressed in ovarian cancer tissue than it was in normal tissues.

Finally, the researchers examined if the viral microRNA influenced the course of the disease. One viral microRNA of the herpes simplex virus 2, miR-H25, was linked with improved outcomes for ovarian cancer.

“In women with expression of miR-H25 the disease was less aggressive,” Dr. Ferlini said. “We cross validated these findings in another data set using a method called in situ hybridization and found the same results, which provides strong proof of concept that this microRNA is working to stimulate a better immune response against the cancer.”

In contrast, they found that a viral microRNA of the Epstein Barr virus, miR-BART7 worked to stimulate the activity of a specific enzyme (ADH1B), making the platinum-chemotherapy used to treat ovarian cancer less effective.

“This research is opening a new door. To date, viral microRNAs were not considered in cancer patients,” Dr. Ferlini said. “We can use the fact that there are some viral components inside cells to help personalize cancer treatments.”

About Western Connecticut Health Network
Western Connecticut Health Network is the region's premier, patient-centered health care organization serving residents of Western Connecticut and adjacent New York. With this recent affiliation, the organization is now anchored by three nationally recognized hospitals, Danbury Hospital, New Milford Hospital and Norwalk Hospital, as well as their affiliated organizations. In addition to the three hospitals, the continuum of care offered includes numerous medical practices and sub-specialties across the region, home health care services, a nationally renowned biomedical research institute, the Western Connecticut Health Network Foundation, Norwalk Hospital Foundation, the Norwalk Hospital Foundation and other affiliates. For more information, visit our websites: http://www.danburyhospital.org; http://www.newmilfordhospital.org; and http://www.norwalkhospital.org. For more information, visit TheNewWCHN.org. Share your comments with us at Facebook.com/DanburyHospital; Facebook.com/NewMilfordHospital and/or Facebook.com/NorwalkHospital.

About Cristiano Ferlini, MD, PhD
Dr. Ferlini is a world-renowned physician-researcher in the fields of cancer research and the development of targeted agents and personalized treatments. Before joining the WCHN Biomedical Research Institute as Director of Biomedical Research in 2009, he was a professor of Pharmacogenetics at Catholic University of the Sacred Heart in Italy. He also served as chief of hematology at CSV, Reparto Medicina in Italy. A current clinical professor of Gynecologic Oncology at the University of Vermont, Dr. Ferlini earned a medical degree from the University of Florence and a PhD in immunology from the University of Rome.
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