Researchers Find Gene with Potential Immuno-Oncology Applications

Researchers Find Gene with Potential Immuno-Oncology Applications

Recently, researchers at the University of Cincinnati announced that they had found the human gene DEK in the plasma of patients with head and neck cancer. The discovery has highlighted DEK as a key path for understanding more about the relationship between the body’s immune system and treatment for patients. The finding was presented at the Multidisciplinary Head and Neck Cancer Symposium held at the end of February in Scottsdale, Arizona. Dr. Trisha Wise-Draper, an assistant professor in the Division of Hematology Oncology at the university’s School of Medicine, was the principal investigator on the study. As she explains, head and squamous cell carcinoma is the sixth most common cancer in the world, making it important to identify biomarkers that can point to better treatment modalities.

Why Scientists Are Interested in DEK

Other researchers have linked infection with human papilloma virus (HPV) to specific outcomes for head and neck cancer, which has led to more effective and less intense treatment plans for many patients. However, no plasma biomarker currently exists for predicting tumor response or the possibility of a relapse. The DEK gene, which has been shown to promote cancer, is highly expressed in tissue specimens from various types of tumors, including breast cancer, melanoma, and head and neck cancer, as evidenced by the presence of DEK RNA and protein. In addition, DEK RNA and protein is also present in patients with autoimmune diseases, suggesting that the gene has played a role in the body’s immune response.

White blood cells secrete DEK protein, which has caused scientists to wonder whether DEK is present in the plasma of patients with cancer and, if so, if it could be used to make correlations with patient outcomes and disease aggression. Dr. Wise-Draper and her team have shown that DEK is present in concentrated amounts in head and neck cancer tissue at all tumor stages and regardless of HPV infection. To address the research question, whole blood from patients who have received a head and neck cancer diagnosis, but who not yet begun treatment, along with that of age-matched healthy adults, was collected. Then, researchers removed plasma from separated samples and used an enzyme-linked immunosorbent assay (ELISA) to test for the presence of DEK proteins. The ELISA test uses antibodies and color changes to help identify an unknown substance.

The Study’s Findings and Implications

Image courtesy MIKI Yoshihito | Flickr

The study confirmed that DEK was present in the plasma of patients with head and neck cancer, as well as in patients who are healthy. However, patients with cancer had lower levels of DEK, and the team found an inverse correlation with levels of interleukin-6 in the plasma. Interleukin-6 is secreted by T-cells, which are leukocytes that are fundamental to the immune system. In fact, this substance typically triggers an immune response.

Dr. Wise-Draper concluded that the newly discovered link between interleukin-6 and DEK could suggest that patients with high levels of DEK could have better outcomes. In the context of immuno-oncology, this finding may mean that patients with high levels of DEK in their plasma may respond more effectively to immunotherapy. In order to test whether this finding could have clinical applications, her team is performing analyses to find correlations between DEK and the body’s natural immune response, as well as reactions to various treatments. In addition, she is interested in identifying any link between DEK in the serum and early relapse.

The University of Cincinnati’s finding could have major implications for the future of personalized and targeted treatments for people with head and neck cancer. With virtually no biomarkers currently accepted to direct treatment approaches, DEK could help create customized treatment plans in the way that HPV diagnoses have helped determine the most appropriate therapies. DEK has also been suggested in immuno-oncology treatment for other cancers. In 2014, researchers suggested that it could serve as a potential marker for aggressive phenotype and irinotecan-based therapy response in patients with metastatic colorectal cancer. DEK apparently plays some role in cancer growth and death in colorectal cancer when it is overexpressed. Thus, DEK plasma measurements could have implications for treatment modalities in patients with cancers other than head and neck squamous cell carcinoma.

DEK’s Role in the Human Body

DEK plays a very complex role in the body. Scientists have long linked it to cancer, finding that it is often an overexpressed and even amplified, gene in human cancers. However, researchers have also found that DEK proteins play a role in repairing breaks in the double-stranded structure of DNA. DEK depletion in human cancer cell lines and xenografts was shown to induce a DNA damage response, as demonstrated by the presence of gamma-H2AX and FANCD2. This link to DNA could also have some bearing on its usefulness for the field of immuno-oncology.

Scientists have known for a long time that DEK is closely linked to several DNA processes. For example, the DEK protein binds to both cruciform and superhelical DNA and can create closed circular DNA from positive supercoils. During mRNA processing, the DEK protein also plays a role in identifying splice sites.

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