A Better Way to Spot Disease

Tiny pieces of RNA are turning out to play a big role in health. Over the past few years, scientists have found that these molecules, called microRNAs, are involved in key functions in cells and are linked to the development of certain cancers and other diseases. A new study led by scientists at Nanjing University, in China, finds that microRNAs circulating in blood can serve as a molecular “fingerprint” for cancers and diabetes. The findings raise the possibility that a simple blood test could help clinicians tailor treatments to individual patients.

MicroRNAs are tiny strands of RNA molecules that do not code for proteins as messenger RNAs do; instead, they bind to messenger RNA to help control the synthesis of proteins. Over the past few years, studies have found that microRNAs affect the way that genes are expressed in cells, and have linked specific microRNAs to particular cancers. Studies in recent months have shown that individual microRNAs associated with prostate cancer and lymphoma can be found circulating in the bloodstream. This would be a boon to oncologists, who currently rely primarily on expensive imaging and invasive biopsies.

In a new paper, published in Cell Research, scientists give the first comprehensive tally of microRNAs in blood serum and identify patterns of microRNAs that distinguish patients with two kinds of cancer and diabetes from healthy subjects. The researchers used sequencing technology to identify the type and levels of microRNAs in the blood serum of healthy people, and they found that these measurements are consistent from individual to individual. Next, they looked at the types of microRNAs and the levels in patients with lung cancer, colorectal cancer, and diabetes. For each condition, the researchers identified a unique pattern of microRNA expression that differed from that of healthy people.

Lead author Chen-Yu Zhang says that many scientists were surprised to discover that microRNA can be measured in blood serum, because the blood also contains ribonuclease, an enzyme that digests RNA. Although it’s not yet clear how microRNAs escape destruction and persist in the blood, Zhang says, “whatever the reason, microRNAs are stable in the serum and are resistant to ribonuclease digestion.”

Frank Slack, a molecular biologist at Yale University, who was not involved in the study, says that microRNA molecules have been causing a stir among cancer researchers because “their expression patterns seem to give a pretty accurate indication of what type of cancer a patient might have, as well as indicating the potential prognosis of that patient.” In fact, microRNAs seem to provide a more specific indicator of cancer type than measuring all the genes expressed in a tumor. However, the usefulness of measuring microRNA is limited if it requires sampling tumors directly. Scientists have been hunting for ways to detect cancer more quickly and easily using biomarkers in the blood or other bodily fluids. Slack says that recent studies showing that microRNAs can be detected in blood are exciting because they suggest that “you might be able to get that same information just from getting the blood from that patient.”

Furthermore, Slack says, the Cell Research paper shows that microRNAs have patterns in diabetes and could be useful in other diseases that involve similar changes to microRNA. He says that such a blood marker would be particularly desirable in “diseases where you don’t know the site of action or the lesion in the body.” Even in a condition like diabetes, for which biomarkers exist, microRNAs might provide missing information, such as predicting a person’s susceptibility, Slack adds.

Zhang says that spotting several different microRNAs specific to a disease would offer an advantage over relying on one or two biomarkers, which are not always present in individual cases. Such a biomarker could also be used to track a disease’s progression over time and to evaluate a patient’s response to a treatment. Zhang says that a patient’s specific pattern of blood microRNAs could also serve as the basis for more personalized medicine, helping doctors distinguish between different forms of a disease or patients who are likely to respond differently to a drug.

The current study relied on expensive sequencing technologies, but Zhang says that eventually, microarrays could measure key microRNAs in the blood much more cheaply–tests that biotech companies are already beginning to develop. Slack says that microRNA is “a new kind of marker that will be emerging in the next decade or so” but that controlled studies are needed to see whether microRNA patterns provide reliable predictions about individual patients and also apply to a wide range of diseases.