Researchers Present Findings at 2016 TRIO Combined Sections Meeting

by Thomas R. Collins •

Investigators from around the country and Canada presented their findings at the Triological Society Combined Sections Meeting, held in January in Miami Beach, Fla. Here are some research highlights from the event.

Causal Network Analysis of Head and Neck Keloid Tissue Identifies Potential Master Regulators

Researchers using DNA analysis and a sophisticated analysis of published literature have found four “master regulators” in charge of four molecular networks that appear to be involved in the development of keloid tumors, offering up future areas of focus for the development of therapies for these hard-to-eliminate lesions.

Keloids are benign fibroproliferative tumors more commonly found in people with darker skin, including African-Americans and Asians. They have an incidence rate of 4% to 16%. One of the most troublesome aspects of keloids is that they recur so frequently after treatment, said Laura Garcia-Rodriguez, MD, a fourth-year resident at Henry Ford Health System in Detroit. “Not only are they aesthetically displeasing, [but] they can cause pain, pruritis, and loss of function,” she said. “The problem with keloids is that there can be up to a 50% recurrence rate. It’s something very hard to explain to a patient who has a very large keloid on [his or her] face.”

Researchers extracted DNA from six keloid tissue samples and six normal tissue samples, then performed genome-wide profiling, finding 152 genes that were differentially methylated between the keloid tissue and the normal tissue.

The 10 with the highest statistical significance were analyzed using causal network analysis (CNA) to find networks with directionality that connect upstream regulators with downstream expression products. The CNA is part of the Ingenuity Pathway Analysis software that includes a database of about five million observations from published literature.

The researchers identified four master regulators and 19 intermediate regulators. A master regulator is a gene or drug positioned as the central or master hub that has the ability to command or influence downstream events, Dr. Garcia-Rodriguez said. She likened master regulators to the conductors of an orchestra and intermediate regulators to individual instruments in an orchestra. The master regulators identified (the chemical drugs tributyrin and pyroxamide, which the analysis showed are likely activated in the relevant networks, and the molecules PRKG2 and PENK, which were predicted to be inactivated) all appear to relate back to tumor protein 53 (TP53), a tumor suppressor.

Inactivation of the p53 tumor suppressor is a frequent event in the development of tumors, and alterations or mutations in the gene are reported to occur in almost every type of cancer, at rates varying between 10% (in hematopoietic malignancies) and close to 100% (in high-grade serous carcinoma of the ovary).