USA researchers study significance of RAB genes in pancreatic cancer

Shashi Anand, Ph.D., a postdoctoral fellow in pathology, is the lead author of a study on the potential prognostic significance of RABs in pancreatic cancer.

A group of researchers and physician-scientists from the USA Health Mitchell Cancer Institute along with University of South Alabama College of Medicine faculty in the Department of Pathology and Department of Biochemistry and Molecular Biology are studying how certain genetic abnormalities affect the progression of pancreatic cancer. They recently published a research article titled “Comprehensive Analysis of Expression, Clinicopathological Association and Potential Prognostic Significance of RABs in Pancreatic Cancer” in the International Journal of Molecular Sciences.

According to the National Cancer Institute, pancreatic cancer is the third leading cause of cancer-related death in the United States. “Poor clinical outcome of pancreatic cancer is mostly due to its late diagnosis and lack of effective therapies, emphasizing the need to identify novel biomarkers and therapeutic targets for effective disease management,” said Shashi Anand, Ph.D., a postdoctoral fellow in pathology and the lead author of the article. “Several genetic aberrations have been identified in pancreatic cancer that drive its malignant progression. However, we have not succeeded in translating the existing information into effective therapies.”

Thus, finding novel differentially expressed genes in pancreatic cancer and understanding their role in biology holds the potential to improve pancreatic cancer diagnosis, prognosis and treatment, Anand said.

Ajay Singh, Ph.D., professor of pathology and senior author of the study, explained that all human cells are comprised of various membrane-bounded compartments that interact with the cells’ surroundings. Cells release their internally synthesized biomaterial into the extracellular matrix via exocytic pathways, or they internalize the material from the environment to the inside of the cell via endocytic pathways.

Shashi Anand, Ph.D., left, works in the lab of Ajay Singh,
Ph.D., right, at the Mitchell Cancer Institute.

“This bi-directional communication between the cells and their external environment is crucial for optimal tissue and organ functions,” Singh said. “A specific set of closely related proteins, named RAB GTPases, controls this vesicle trafficking by acting as regulatable switches in response to the cellular needs and external cues. The abnormal function of RAB proteins, resulting from genetic changes and aberrant transcriptional activation, can cause a disease state including the promotion of carcinogenesis.”

In the published study, Anand analyzed the expression of 62 RAB genes in hundreds of pancreatic cancer patients using The Cancer Genome Atlas database. The study identified 10 RAB genes that exhibited significant differences in expression between normal and cancerous pancreatic tissues. In addition, differential RAB expression was also correlated with patient’s race, drinking habits, and prior diagnosis of diabetes and pancreatitis. A significant association of transcript levels of some of the RAB genes with the survival predictability of pancreatic cancer patients was also recorded. Additionally, Anand identified low-frequency genetic mutations, amplifications and deletions of RAB genes in pancreatic cancer.

“These are very important early findings suggesting the potential diagnostic and prognostic significance of RABs in pancreatic cancer,” said Moh’d Khushman, M.D., a medical oncologist at the Mitchell Cancer Institute and a co-author of the article. “Further investigations on their functions and underlying mechanisms can also provide important leads for the development of mechanism-based therapies.”

The work outlined in the research paper was supported by the National Institutes of Health grant funding and internal support from the Mitchell Cancer Institute.

Anand is a postdoctoral fellow in the laboratory of Singh, who leads the cancer biology program at the Mitchell Cancer Institute. He received his graduate degree from CSIR-Institute of Microbial Technology, India. He is the recipient of a senior research fellowship from the Council of Scientific and Industrial Research, a federal research agency in India.