Survey of Pancreatic Tumors Reveals microRNA Signatures
Taking a new approach to a devastating disease, researchers have developed molecular signatures for pancreatic tumors that might one day help physicians diagnose and treat the fatal cancer.
They did so by profiling the activity of microRNAs, short RNA molecules that regulate the activity of genes. These snippets of genetic material appear to control important biological processes, including some related to cancer. microRNA signatures have been developed for many types of cancer and used experimentally to classify tumors.
The researchers, led by Dr. Carlo Croce of Ohio State University (OSU), conducted a series of experiments to see whether profiling microRNAs in pancreatic tumors could provide useful information for physicians and patients. The results were positive but preliminary.
They identified distinct patterns of microRNA activity that could distinguish pancreatic cancer from corresponding normal tissue in 90 percent of cases. And a subset of microRNAs was more often found in tumors from patients who survived longer than 24 months compared with those who did not.
Pancreatic cancer is often diagnosed after it has spread to other tissues, and many patients die within a year of diagnosis.
The researchers caution that the findings, published today in the Journal of the American Medical Association (JAMA), need to be validated in prospective studies. But the results add to the growing evidence that microRNAs may play a role in many, if not all, cancers and could be used in diagnosis and treatment.
"This is the first step of many in trying to understand the role of microRNAs in pancreatic cancer," says first author Dr. Mark Bloomston of OSU. "But this study tells us that microRNAs are important in this disease, too."
microRNAs are in the news. Three studies in this week's Science describe mice that were engineered to lack certain microRNAs, with dramatic effects on their health. Some animals died of heart failure and others were unable to fight off infection because of weakened immune systems.
"It's clear that microRNAs are very important in normal development and differentiation," says Dr. Croce, whose laboratory has profiled a number of cancers. "And it's also clear that the deregulation of microRNAs can lead to cancer."
Some microRNAs are deregulated in multiple types of tumors. One example is mir155, which is the focus of two studies in Science and is altered in some pancreatic cancers.
The diverse biological functions of microRNAs are only just beginning to be understood, but defects involving microRNAs and cancer are well documented. Certain microRNAs control genes that normally suppress tumors or that drive cancer (oncogenes).
The hope for microRNAs in pancreatic cancer, says Dr. Bloomston, is that physicians might one day use molecular profiling to identify the patients most likely to benefit from surgery or from aggressive treatments.
Another use would be early detection. Physicians might profile microRNAs to monitor new lesions in the pancreas and premalignant conditions (such as chronic pancreatitis) in patients at high risk of the disease, such as those with a strong family history of pancreatic cancer.
An accompanying editorial in JAMA says that the study provides a glimpse of the future of clinical oncology.
"This is a remarkable discovery with wonderful promise for diagnostics and therapeutics in what is a devastating disease," says co-author Dr. Scott Waldman of Thomas Jefferson University, who studies biological markers and cancer.
But like the OSU researchers, he emphasizes that the discovery of microRNA fingerprints in pancreatic tumors is really the first step in a long process of translation and validation.
"It is important for people to understand that there is no shortcut," says Dr. Waldman, noting that many promising biomarkers for cancer have failed along the way.
At least one previous study provides support for the new findings. In January, another group at OSU described molecular signatures for pancreatic tumors in the International Journal of Cancer. Working independently, the OSU groups used different technologies and patient samples, but reached similar conclusions.
"Many of the microRNAs we identified as important were on their list," says lead investigator Dr. Tom Schmittgen, who collaborated with researchers from the University of Oklahoma Health Sciences Center."It's always reassuring to know that your results have been reproduced," he adds. His laboratory is now working with Dr. Croce's on diagnostic tools and ways to inhibit microRNAs in cancer cells.
By Edward R. Winstead