An international team of scientists has identified a gene associated with aggressive liver cancer, which could lead to more targeted therapies. The finding also represents another step toward precision cancer treatment.
Led by National University of Singapore, the team found that patients with hepatocellular carcinoma express SALL4, a stem cell gene expressed in human fetuses but inactive in noncancerous adults.
Hepatocellular carcinoma is the most common form of liver cancer and the third leading cause of cancer-related deaths worldwide. Though incidence rates are highest in Asia and sub-Saharan Africa, rates in the U.S. and northern Europe are increasing steadily.
The findings were published in the New England Journal of Medicine in June, along with an editorial outlining the significance. Primarily, SALL4 could help identify liver cancer patients who need treatment most and would benefit from an aggressive treatment regimen.
"Now you can use SALL4 as a biomarker," said Dr. Snorri Thorgeirsson of the National Cancer Institute, who co-authored the editorial. "If you find patients who overexpress this gene, you can focus treatment on them."
The research team studied tissue samples from about 400 liver cancer patients in Singapore and Hong Kong. Half of the patients expressed low levels of SALL4 while 10-20 percent expressed high levels of the gene. The team then established SALL4 as an independent marker for diagnosis of hepatocellular carcinoma and found that blocking the gene played a role in stopping the cancer’s spread.
SALL4 previously was associated with leukemia as well as ovarian, endometrial, gastric, breast and lung cancers. Those patients, too, could see more personalized treatment options because of the team’s work.
The editorial called the findings “convincing” but said more study is needed to determine if targeting SALL4 alone can yield treatments that prevent cancer from recurring.
The editorial concluded: "Clinical translation of these important findings is urgently needed to achieve individualized therapies and ultimately improve the poor outcome in patients with hepatocellular carcinoma."
The study was conducted in collaboration with Brigham and Women’s Hospital in Boston, Harvard Stem Cell Institute in Cambridge, National University Health System in Singapore, Queen Mary Hospital in Hong Kong, and Queen’s University Belfast in the United Kingdom. The National Institutes of Health funded part of the research.