Two Proteins Identified as Markers of Response to Neoadjuvant Chemotherapy for Ovarian Cancer
Researchers from the Danbury Hospital Biomedical Research Institute have discovered that high expression levels of two proteins - HGF and c-MET - are present in women with ovarian cancer who did not benefit from undergoing tumor-shrinking chemotherapy therapy prior to having surgery to remove their tumor.
Marisa Mariani, PhD, of Danbury Hospital Biomedical Research Institute, and colleagues, who published their results in OncoTarget, made this discovery using a two-pronged approach that first explored possible markers of chemotherapy resistance at the microRNA and gene expression level, and then validated any markers of interest at the protein level.
"This approach is important because if you are eventually going to use a drug to target these markers, the drug will target the protein and not the gene," Dr. Mariani said. "We had to confirm that what we were seeing at the gene level lead to a change at the protein level."
Ovarian cancer is the leading cause of death for gynecologic malignancies. About 85 percent of women who are diagnosed in the advanced stage of the disease will die. Women with advanced disease may sometimes undergo chemotherapy prior to surgery, called neoadjuvant chemotherapy, in an attempt to shrink the tumor.
Exposing the tumor to chemotherapy prior to surgery, gave Dr. Mariani and colleagues a unique opportunity to investigate the biology of the tumor's response to chemotherapy. Using tumor samples taken from patients with ovarian cancer after neoadjuvant chemotherapy, they discovered several prevalent microRNAs, the presence of which demonstrated an ability to survive even after exposure to chemotherapy. Among the discovered microRNA miR-193a-5p was the most significant.
MicroRNA regulates the expression of genes. Therefore, the researchers next conducted an analysis to determine the targets of miR-193a-5p and found that two genes, HGF and cMET, were significantly correlated with the microRNA.
Finally, the researchers used quantitative fluorescent immunohistochemistry to conduct a protein analysis. Once again they found that protein expression levels of HGF and cMET expression were significantly increased in patients after undergoing neoadjuvant chemotherapy. In fact, patients who relapsed shortly after neoadjuvant chemotherapy had the highest levels of HGF and cMET and those patients who responded best to the treatment had the lowest expression levels.
"This type of discovery is very important because if patients undergo neoadjuvant chemotherapy and the treatment has no effect, than it is often too late to perform surgery because the cancer has progressed," said senior author Cristiano Ferlini, MD, PhD, also from Danbury Hospital Biomedical Research Institute. "This can help us to know upfront that these patients may not benefit from neoadjuvant therapy and can prevent them from undergoing this unnecessary treatment."
According to Dr. Ferlini, the Danbury Hospital Biomedical Research Institute will continue to embrace cutting-edge technology, working to uncover biomarkers that will help clinicians to more appropriately select therapies for patients with cancer.
"Even though we are a small organization we have been very successful operating at the border between clinical and basic research," Dr. Ferlini said. "We are motivated to learn from our patients at the bedside and get back to the bedside as quickly as possible with new treatment options."
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, 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.