RNA Patterns May Aid Diagnosis of Pancreatic Cancer

COLUMBUS, Ohio, May 1 -- To distinguish between pancreatic cancer and pancreatitis, clinicians may soon be able to turn to the expression patterns of short strands of RNA -- so-called microRNAs.

Analysis of microRNAs (also known as miRNAs) -- strands of ribonucleic acid that regulate the expression of some genes -- has also found at least one that appears to be a marker for poor survival in pancreatic cancer, according to Mark Bloomston, M.D., of Ohio State University.

"We have identified -- we believe for the first time -- a global expression pattern of miRNAs that can differentiate ductal adenocarcinomas of the pancreas from normal pancreas and chronic pancreatitis with 95% accuracy," Dr. Bloomston and colleagues reported in the May 2 issue of the Journal of the American Medical Association.

However, they said, the data are preliminary and will need to be validated in others studies.

Indeed, such research is "just the beginning in the continuum connecting discovery to clinical application," noted Scott A. Waldman, M.D., Ph.D., of Thomas Jefferson University in Philadelphia, and Andre Terzic, M.D., Ph.D., of the Mayo Clinic in Rochester, Minn., in an accompanying editorial.

They characterized the work of Dr. Bloomston and colleagues as "seminal" but said full-scale clinical trials will be needed before the observations can be put into everyday practice.

Nevertheless, they said, the results "reinforce the usefulness of these biomarkers in defining the molecular taxonomy of tumors."

MiRNAs may also be useful for defining prognosis and identifying low- and high-risk populations of patients with pancreatic cancer, they added. And they may point the way to new therapeutic targets -- "a critical unmet clinical need in the management of pancreatic cancer."

Dr. Bloomston and colleagues used microarray technology to analyze RNA from 65 patients with ductal adenocarcinoma of the pancreas and 42 with chronic pancreatitis. For all the patients, they also analyzed the microRNA expression from adjacent normal tissue.

The researchers found:

• 21 microRNAs whose expression was increased and four with decreased expression that correctly differentiated pancreatic cancer from benign pancreatic tissue in 90% of samples.
• 15 over-expressed and eight under-expressed miRNAs were able to differentiate pancreatic cancer from chronic pancreatitis with 93% accuracy.
• A set of six microRNAs distinguished long-term survivors with node-positive disease - those who lived more than two years after resection -- from those dying within 24 months.
• One of those, dubbed miR-196a-2, was found to predict poor survival: Those with high expression of the miRNA lived a median 14.3 months, compared to 26.5 months for those with low expression. The difference was statistically significant at P=0.009.

Little is known about the function of many of the miRNAs turned up by the study, Dr. Bloomston and colleagues said, but two -- miR-21 and miR-155 - were "uniquely over-expressed" in cancer tissue compared with normal pancreas or chronic pancreatitis.

The first is thought to play a role in preventing programmed cell death and is found in several solid tumors, while the second is also over-expressed in solid tumors as well as being associated with lymphomas.