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Danbury Hospital Researchers Find Viruses Could Affect Cancer Outcomes

Dr. Cristiano Ferlini made a discovery about the relationship between an early contracted virus and its affect on cancer outcomes.
Dr. Cristiano Ferlini made a discovery about the relationship between an early contracted virus and its affect on cancer outcomes. Photo Credit: http://www.danburyhospital.org/

DANBURY, Conn. -- Researchers from the Western Connecticut Health Network Biomedical Research Institute in Danbury 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.

Dr. Cristiano Ferlini, 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,” Ferlini said. “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 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,” 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,” Ferlini said. “We can use the fact that there are some viral components inside cells to help personalize cancer treatments.”

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