Scientists at the Johns Hopkins University School of Medicine say a simple blood test based on detection of tiny epigenetic alterations may reveal the earliest signs of pancreatic cancer. The findings of their research, if confirmed, they add, could be an important step in reducing mortality from the cancer, which has an overall five-year survival rate of less than 5% and has seen few improvements in survival over the last three decades.
“While far from perfect, we think we have found an early detection marker for pancreatic cancer that may allow us to locate and attack the disease at a much earlier stage than we usually do,” explains Nita Ahuja, M.D., an associate professor of surgery, oncology and urology at the Johns Hopkins and leader of the study (“Novel Methylation Biomarker Panel for the Early Detection of Pancreatic Cancer”) described online this month in the journal Clinical Cancer Research.
For their study, Dr. Ahuja and her colleagues focused on two genes.
“We used a nanoparticle-enabled MOB (Methylation On Beads) technology to detect early-stage pancreatic cancers by analyzing DNA methylation in patient serum,” wrote the investigators in their journal article. “We identified two novel genes, BNC1 (92%) and ADAMTS1 (68%), that showed a high frequency of methylation in pancreas cancers (n=143), up to 100% in PanIN-3 and 97% in Stage I invasive cancers.”
Together, BNC1 and ADAMTS1 were detectable in 81% of blood samples from 42 people with early-stage pancreatic cancer, but not in patients without the disease or in patients with a history of pancreatitis, a risk factor for pancreatic cancer.
Dr. Ahuja’s team found that, in pancreatic cancer cells, it appears that chemical alterations to BNC1 and ADAMTS1, i.e., epigenetic modifications that alter the way the genes function without changing the underlying DNA sequence, silence the genes and prevent them from making their protein product, the role of which is not well understood. These alterations are caused by the addition of a methyl group to the DNA.
Using MOB, the researchers were able to single out in the blood even the smallest strands of DNA of those two genes with their added methyl groups. The technique uses nanoparticle magnets to latch on to the few molecules being shed by the tumors, which are enough to signal the presence of pancreatic cancer in the body, the researchers found.
Dr. Ahuja says the practical value of any blood test for cancer markers depends critically on its sensitivity (meaning the proportion of tumors it detects) and its specificity (meaning how many of the positive results are false alarms). The specificity of this new pair of markers is 85%, meaning 15% would be false alarms. She hopes further research will help refine the test, possibly by adding another gene or two, in order to go over 90% in both sensitivity and specificity.