Scientists at the National University of Singapore (NUS) have discovered a biomarker that may improve the diagnosis, prognosis, and treatment of esophageal squamous cell carcinoma (ESCC), the major histological form of esophageal cancer and the leading cause of cancer death worldwide.
Called adenosine deaminase acting on RNA-1 (ADAR1), the new biomarker was discovered by a team lead by Polly Chen, MD, PhD, a research assistant professor at the NUS Cancer Science Institute of Singapore. The team is also the first to demonstrate that the editing of protein-making sequences promotes the development of ESCC. The study findings were first published online in Cancer Research on 4 December 2013.
ESCC patients currently have a poor prognosis, with an overall five-year survival rate ranging from 20% to 30%. Clinicians have indicated an urgent need for biomarkers that can diagnose the disease as early as possible, estimate patient reaction to chemotherapy or radiotherapy, and predict the overall survival rate of patients undergoing treatment.
In normal human cells, deoxyribonucleic acid (DNA), which comprises the genetic code, serves as a template for the precise production of ribonucleic acid (RNA) such that the DNA code and RNA code are identical. Editing is a process in which RNA is changed after it is made from DNA, resulting in an altered gene product. Such RNA editing is likely to play a role in the formation of tumors, either by inactivating a tumor suppressor or by activating genes that promote tumor progression.
In their study, the NUS researchers discovered that the RNA editing enzyme ADAR1, which catalyzes the editing process, is significantly overexpressed in ESCC tumors. They observed that ADAR1 changes the product of the AZIN1 protein to a form that promotes development of the disease. Clinically, the overexpression of ADAR1 in ESCC tumors was correlated with shorter survival times for ESCC patients.
The study findings suggest that ADAR1 can serve as a useful biomarker to detect disorders leading to ESCC and as a potential therapeutic target. The study may also provide the key to a biological process for drug development in the treatment of ESCC.
“Investigating the connection between ADAR1-mediated RNA editing and cancer progression is only the initial step in this research,” said Chen. “The tumoral overexpression of ADAR1 can be used as an early warning sign of ESCC, and halting or reversing the process may block the cells’ conversion from normal to malignant.”
Moving forward, the researchers will further investigate the key RNA editing events regulated by ADAR1 during ESCC development. They plan to develop a method to correct the RNA editing process through restoring ADAR balance by silencing ADAR1 and reinstating a specific hyperedited or hypoedited transcript.
For complete study findings, visit Cancer Research.
