“A simple blood test that could act as a "crystal ball" to detect early signs of cancer could be tested on patients within two years,” reported The Daily Telegraph . It said scientists have found that small pieces of genetic material called microRNAs are released by prostate cancer cells into the blood. These can be detected more easily than proteins, “providing an opportunity for earlier diagnosis”. This type of test could potentially detect other types of cancer.
This report is based on a study looking at microRNAs in the blood of healthy men and men with metastatic prostate cancer, as well as tests in mice transplanted with human prostate cancer cells. It demonstrates what could be a promising new method for detecting cancer, and specifically shows a capacity for identifying men with metastatic prostate cancer. This is an advanced stage in the disease, at which point treatments are unlikely to extend the life of the patient. Further, larger studies are needed to confirm these findings, and to assess whether the test can detect prostate cancer at earlier stages.
Where did the story come from?
Dr Patrick Mitchell, Rachael Parkin, Evan Kroh and colleagues from the Fred Hutchinson Cancer Research Center and other research centres and health care systems in the US carried out the research.
The study was funded by the Pacific Ovarian Cancer Research Consortium/Specialized Program of Research Excellence in Ovarian Cancer, the National Cancer Institute, the Pacific Northwest Prostate Cancer Specialized Program of Research Excellence, the Core Center of Excellence in Hematology, and the Paul Allen Foundation for Medical Research. It was published in the peer-reviewed scientific journal: Proceedings of the National Academy of Sciences of the USA.
What kind of scientific study was this?
This was an experimental laboratory study looking at whether blood contained small RNA molecules called microRNAs (miRNAs), and whether these molecules could be used to identify people with cancer. RNA is a molecule similar to DNA (both are nucleic acids), and miRNAs play a role in regulating whether genes produce proteins or not. The levels of certain miRNAs have been found to be altered in cancerous tissue, therefore the researchers thought these changes might be detectable from blood samples.
The researchers took healthy human blood and spun it at high speeds in a special machine to separate the blood cells from the fluid that carries them around the body (called plasma). They then looked at the sizes of nucleic acid molecules present in the plasma, and tested whether these molecules were DNA or RNA. The sequence of these molecules was then examined and compared with the sequence of known miRNA molecules.
RNA molecules are generally quite unstable and break down easily, and if miRNA molecules are to be used in monitoring cancers, they would have to be relatively stable in order for the tests to be reliable. Therefore, the researchers tested the stability of three different blood miRNAs (called miR-15b, miR-16, and miR-24) from blood were by subjecting plasma to different conditions that would normally cause RNA to break down, such as leaving it at room temperature for 24 hours, or freezing and thawing it several times. They also looked at whether these three miRNAs could be detected at similar levels in serum, which is the liquid that remains when blood is allowed to clot.
The researchers then wanted to test whether miRNAs produced inside tumour cells could be found in blood. To do this they took 24 mice and injected half of them with human prostate cancer cells and used the other half as controls. Blood was then taken from the mice, and the levels of different miRNAs were examined, including some that were only found in the human tumour cells but not in mice (miR-629* and miR-660). Also examined were miRNAs that were found in both the human tumour cells and in the mice (non-tumour specific miRNAs).
In order to identify miRNAs that could be useful in detecting cancer, the researchers needed to find those that were found at moderate or high levels in tumour tissue, but at very low or undetectable levels in the plasma of healthy humans. To do this, they compiled a list of miRNAs that have been found in human prostate cancer cells in other studies, and then ruled out those that had also been found in the normal human plasma in their first experiment. When they had identified some possible candidates, they compared the levels of these candidate miRNAs in pooled serum samples from 25 men with metastatic prostate cancer (cases), and from 25 healthy men of the same ages (controls). Once they had identified miRNAs that had higher expression in the pooled cancer serum, they looked at each serum sample individually.
What were the results of the study?
The researchers found that normal human blood plasma and serum did contain known miRNAs, and that the three miRNAs they tested did not break down when left at room temperature or subjected to freezing and thawing. The levels of non-tumour specific miRNAs in plasma did not differ between mice injected with human prostate cells and mice which had not been injected with these cells (the controls). However, the researchers found human tumour miRNAs in the plasma of all 12 mice injected with the prostate cancer cells, but in none of the 12 control mice. This showed that miRNAs produced in tumour cells could enter the blood and be detected by a blood test.
From looking at the results of other studies and their own tests, the researchers identified six miRNAs that had been reported as present in human prostate cancer cells, but not in normal human plasma or serum. They found that the levels of five of these six miRNAs were increased in pooled serum from 25 men with metastatic prostate cancer (cases) compared to pooled serum from healthy men (controls). Among these five miRNAs, one called miR-141 showed the greatest difference between case and control serum. The researchers found that testing levels of this miRNA identified six out of every 10 men with metastatic prostate cancer, meaning that four out of every ten men with metastatic cancer were missed by this test. They found that none of the healthy men would be wrongly considered to have metastatic prostate cancer based on their test results (no false positives).
What interpretations did the researchers draw from these results?
The researchers concluded that miRNAs are found in human plasma, and are remarkably stable. Levels of the miRNA miR-141 can be used to differentiate between blood samples from men with metastatic cancer and healthy men. They say that their results “establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer”.
What does the NHS Knowledge Service make of this study?
These findings point towards a promising new way of detecting cancer using microRNAs. At present, these initial results specifically show the capability of this technique to identify men with metastatic prostate cancer. This is an advanced stage in the disease, at which point treatments are unlikely to extend the life of the patient. More tests will be needed to confirm these findings in a larger sample of men, to assess whether this test will be able to detect prostate cancer at earlier stages, and to compare it to other tests, such as the PSA test, before it becomes widely used. In addition, further research will be needed to identify other miRNAs that may be useful in detecting other types of cancer.
Sir Muir Gray adds...
This is the type of test that could be useful, based on good science. Now the test needs testing.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 29 July 2008
Links to the science
Proc Nat Acad Sci USA 2008; Jul 28 [Epub ahead of print]