Researchers at CHA Bundang Hospital said they have found for the first time in the world that ADAM9 (A Disintegrin and Metalloproteinase 9) can predict the response to treatment early in chemotherapy for liver cancer.
ADAM9 is an enzyme that breaks down proteins and disrupts the body's immune system by cutting off MICA (MHC class I-related chain A), the natural killer cell receptors, expressed on the surface of cancer cells. The team also confirmed that the enzyme has an association with survival prognosis.
MICA, a protein expressed on the surface of abnormal cells, including cancer cells, stimulates and helps NK cells recognize cancer cell antigens and effectively remove them. Therefore, when MICA is cut from the surface of cancer cells by ADAM9, NK cells cannot detect cancer cells, making it difficult for them to remove cancer cells effectively.
To investigate the relationship between ADAM9 expression pattern and cancer progression in patients with liver cancer, the team, led by Professor Lee Jo-ho at the hospital, analyzed genomic data of 370 patients with liver cancer in the cancer genome atlas database and confirmed that ADAM9 expression was higher in liver cancer tissues than in surrounding tissues.
The team also discovered that patients with a higher ADAM9 expression level had a lower survival rate.
In an additional study to confirm their findings, the team divided the liver cancer patients receiving treatment at Bundang CHA Hospital into two groups – a group that received sorafenib as a first-line cancer target therapy, and a group that received nivolumab after failing their first-line treatment – and compared ADAM9 mRNA blood concentration and treatment effect.
As a result, the team found that the ADAM9 blood level increased in the pre-hepatic cancer treatment compared to the general population. In contrast, the ADAM9 blood level was lowered to that of the general population for patients who completely cured their symptoms.
Also, the researchers confirmed that the ADAM9 mRNA blood concentration decreased prematurely in the patient group, showing a therapeutic response after administering the nivolumab.
"The team confirmed a complete response for a patient who had been receiving regorafenib due to the failure of the primary targeted anticancer treatment and NK cell therapy periodically to enhance the treatment efficacy," Professor Lee said. "Notably, sorafenib and regorafenib, which are widely used as treatments for liver cancer, have proved to inhibit the expression of ADAM9 and are expected to bring about synergistic effects when combined therapy with NK cell therapies."
The results of the research were published in the latest issue of the journal Cancer.