New Study by Western Connecticut Health Network Biomedical Research Institute Finds Pivotal Role of Epstein-Barr Virus in Solid Tumors

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Research Indicates Most Common "Mono" Virus Affects Cancer Prognosis

Scientists at Western Connecticut Health Network Research Institute have found that the Epstein-Barr virus—the most common virus found in the human body — is associated with solid tumors and correlates with a poor prognosis in patients with early stage cancer.

The groundbreaking discoveries are detailed in “Epstein-Barr Virus MicroRNA Expression Increases Aggressiveness of Solid Malignancies” in the Sept. 16, 2015 issue of PLOS ONE, a peer-review journal that provides free access to a global audience.

“The implications for treating patients in the future are huge,” said Cristiano Ferlini, MD, director of medical research and Rudy and Sally Ruggles chief of cancer research. “These findings set the stage for further research to develop a blood test to detect the abnormal activation of the Epstein-Bar virus in early stage cancer patients—a move that could lead to personalized treatments that improve survivorship and reduce mortality.”

The study represents the latest milestone for Dr. Ferlini and the Research Institute team since opening five years ago. Ferlini is a world-renowned physician-researcher who has contributed to more than 100 research papers.

“This landmark research reinforces the difference we make when we can apply such advanced findings to the care we deliver,” says John Murphy, MD, WCHN’s president and chief executive officer. “All of our work at the research institute advances medical treatment. What makes a difference, here at home, is how whatever we learn in this community can help not only the people we care for here but also those who are well beyond our reach.”

Mapping the “master switches”
The Epstein-Barr virus is a member of the herpes virus family and is best known as the cause of infectious mononucleosis. Most people get infected with the virus at some point in their lives. Once inside, the virus persists in the body for life and can remain dormant for years or reactivate quietly without causing symptoms.

The scientists at WCHN used raw data from the National Cancer Institute’s Cancer Genome Atlas to perform the first mapping of viral microRNAs among billions of microRNA sequences within cancer and adjacent normal tissues. MicroRNAs—found in human and non-human tissue—are considered the master switches that control cell function.

The Cancer Genome Atlas sequenced microRNAs in human cancers and mapped them to known human microRNAs. WCHN scientists took the federal research one step further by using a “pipeline” software (developed by Deep Pandya, first author of the study) to examine the sequences that were "left over" after this mapping was complete.

“We found that many of those left-over sequences were derived from viruses. Researchers have seen viruses in a variety of human cancers over many decades, but nobody has detailed them at the master switch level until now. These master switches (microRNA) are at the core of what makes cells work and how these cells interact with the immune system across a huge number of tumor types,” said Paul Fiedler, MD, chair of WCHN’s Pathology and Laboratory Medicine and a co-author of the study.

Key findings
The research findings show an active role of Epstein-Barr microRNAs in solid tumors across all types of cancer in both men and women:

  •     The presence of viral microRNA is consistently higher in cancer tissue compared to adjacent noncancerous tissue in all cancer types. Cancer cells weaken the immune system, which allows the previously dormant virus to flourish unchecked. The master switches derived from viruses send signals that further suppress the immune system. “The cancer and the virus share a common goal to turn off the immune system to promote their own survival,” said Fiedler.
  •     The presence of viral microRNA is associated with significantly worse clinical outcomes among patients with early stage cancer. These viral microRNAs may be present in cancer cells or other noncancerous cells embedded within the cancer tissue.
  •     A particular cluster of viral microRNAs is associated with the presence of immune response reaction which inhibits both viral and anticancer immunity. Detecting these specific viral microRNAs may help identify early stage cancer patients who are at risk of poor outcomes. With further research, these patients could be candidates for novel therapeutic strategies such as a class of medications known as immune checkpoint inhibitors.

“Immune checkpoint inhibitors have been recently added to the arsenal of anticancer weapons and are typically used with patients who have late stage cancer. But these medications may be helpful in treating early stage cancer patients who have a high expression of the Epstein-Barr virus,” said Ferlini. “In this manner, we can link cancer treatment and the healing of the immune system to shut down the viral replication and restore an effective anticancer immunity.”

Bench to bedside research
The translational research at the Research Institute focuses on quickly and safely translating promising scientific discoveries from the laboratory into treatments that directly benefit patients at the bedside.

Ferlini keeps the needs of cancer patients and their loved ones upper mind at all times. “To me, a chart with cancer data is a representation of a human tragedy. The lines and dots on a chart represent brothers, sisters, mothers and fathers who are dying. As doctors, we treat patients who we know. But our research can reach thousands of patients who we will never know. It’s one of the best ways to have an impact,” he said.

“Our goal is to get this research to the bedside as soon as possible,” added Ferlini. “We want our discoveries to make a difference in the lives of our patients.”

Here is a full list of the authors: Deep Pandya, Marisa Mariani, Shiquan He, Mirko Andreoli, Manuela Spennato, Candice Dowell-Martino, Paul Fiedler and Cristiano Ferlini.

About the Western Connecticut Health Network Research Institute
The Western Connecticut Health Network Research Institute has joined the ranks of leading research organizations nationwide in the field of molecular science and personalized medicine. The Institute includes a team of renowned scientists known for their groundbreaking work and expertise in various research disciplines. The goal is to advance the health of our community by bringing innovative biomedical research findings to patients in clinical settings as soon and safely as possible.
Located at 131 West St. in Danbury Connecticut, the Institute focuses on Cancer, Cardiovascular and Lyme disease research. The 17,000-square-facility houses state-of-the-art equipment for basic research and complements ongoing research being conducted at the hospital, including clinical trials and epidemiologic studies. Our open style laboratory structure encourages an environment of collaborative research where our scientists with expertise in a myriad of fields, share resources and knowledge across institutional and disciplinary lines.

About the Western Connecticut Health Network
Western Connecticut Health Network (WCHN) is the region's premier, patient-centered health care organization serving residents of Western Connecticut and adjacent New York. WCHN is anchored by three nationally recognized hospitals, Danbury Hospital, New Milford Hospital and Norwalk Hospital, as well as affiliated organizations. In addition to the three hospitals, the continuum of care offered includes numerous medical practices and sub-specialties across the region through the Western Connecticut Medical Group, the Western Connecticut Home Care, the nationally renowned WCHN Research Institute, the WCHN Foundation, the Norwalk Hospital Foundation and other affiliates. For more information, visit TheNewWCHN.org. Share your comments with us at Facebook.com/DanburyHospital; Facebook.com/NewMilfordHospital and/or Facebook.com/NorwalkHospital.

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Andrea Rynn