Discovery of Biomarker for Gastric Cancer Could Improve Treatment

A potential mechanism for the early detection of gastric cancer may lead to better treatment and prognosis.

Changes in RNA sequences plays a key role in the development of gastric cancer, a study published in Gastroenterology found. The findings may lead to earlier detection and better treatment for this disease.

RNA is an intermediate product between DNA and the protein coded by DNA. During RNA’s involvement as a messenger, it undergoes RNA editing, resulting in haywire transmission of information from DNA, leading to an altered gene product with cancer-causing qualities.

In the study, researchers found that the proteins ADAR1 and ADAR2, which play a role in RNA editing, could potentially be used as a biomarker to detect disorders that lead to gastric cancer.

Additionally, the findings suggest that by measuring the editing levels in patient gastric samples, particularly at the pre-malignant stage, may help identify individuals at risk for developing subsequent gastric cancer.

ADAR1 and ADAR2 are upstream regulators that fine-tune the editing of RNAs, however, they have opposing effects on gastric cancer development. While ADAR1 functions as a cancer-promoting gene, ADAR2 functions as a cancer suppressor.

“Currently, most molecular studies on gastric cancer have focused on the alterations in DNA sequences,” said lead researcher Polly Chen. “Despite recent discoveries that shed light on the cancer-causing role of RNA in cancer progression, the alterations in these RNA sequences and its contribution to the development of gastric cancer have not been well studied. Our team is the first to conduct a comprehensive analysis demonstrating that changes in RNA sequences, which are caused by the differentially expressed RNA editing enzymes ADAR1 and ADAR2 in gastric tumors, may serve as a novel driving force for gastric cancer.”

During the study, researchers compared editing levels at different stages of gastric lesions along the normal to cancer continuum. They also examined increasing levels of RNA editing disorder. An additional finding was that patients with developed gastric cancer had the highest levels of ADAR imbalance, which predicted the poorest clinical prognosis.

Normally, DNA alterations occur at the advanced stages of cancer. But with RNA, the editing occurs more frequently, and can be steadily detected in precancerous or premalignant samples at the early stages of the disease. Subsequently, these findings suggest that measuring the ratio of the amount of ADAR1 and ADAR2 present in patients, especially at the early stages of cancer, could be significant in ascribing prognosis for patients with gastric cancer, according to the study.

“The utmost value of this discover stems from its potential to translate into molecular therapy, given that gastric cancer is prevalent in Asia and is one of the most common and deadliest cancers worldwide,” said lead researcher Patrick Tan. “Moving forward, we will further investigate the key RNA editing events driving gastric cancer development and explore safe and efficient methods to correct this process. We are currently looking into designing small molecules such as a specific peptide nucleic acids, which are stable and can be easily delivered to block the cancer-driven RNA editing process.”