New tests find tell-tale signs of cancer in the blood

A new blood test sensitive enough to detect as few as three mutation-bearing molecules could substantially improve cancer diagnosis, according to research published in The Journal of Molecular Diagnostics.

The study, conducted by scientists at Stanford University in California, is one of two new findings that point to an increased role for blood testing in oncology.

The second, by researchers at the VU University Medical Center in Amsterdam, Netherlands, and published in the journal Cancer Cell, demonstrates that RNA found in platelets in the bloodstream can be used to identify lung cancer.

In the Stanford study, a team led by Hanlee Ji developed a new type of blood test called a single colour digital PCR, which can detect DNA mutations released by cancer cells.

In a pilot test using six patients, the blood test, customised for mutation detection, picked up cancer DNA in three of them. The three who returned negative results were all undergoing active treatment at the time, which may have influenced the result.

Ji says the PCR test is potentially useful in detecting a wide range of cancers. There is no blood test for most variants of the disease, and the few that are available are restricted to particular types.

As a result, cancer monitoring is arduous, stressful and expensive.

“Nearly all cancer patients require monitoring by whole body imaging, which can be costly, complex, and time-consuming,” explains Ji.

“In contrast, molecular tests like the one we have developed will enable patients to be monitored at every visit, and thus have the potential for quickly tracking cancer growth and spread.

“Moreover, the test’s rapid turnaround and relatively low cost, especially compared to next-generation DNA sequencing, provide a potential opportunity for universal monitoring of more patients than is currently done.”

As well as being cheaper and faster than existing methods, single colour digital PCR is simple to set up and administer. It requires only a few millilitres of blood. It can be done by a GP and does not require a specialised lab to process.

In the Netherlands study, researchers rejected looking for cancer DNA in favour of looking for its RNA in platelets.

The methodology behind the research is elegant. Platelets are short-lived blood particles that are critical for the blood-clotting and scab-forming processes. However, they also cluster around inflammation and cancer sites.

Platelets have no nuclei themselves and thus contain no DNA. Any RNA they are found to contain must therefore have been absorbed from external sources. In healthy people, this mainly means the cells in bone marrow – known as megakaryocytes – that created them in the first place.

In people with cancer, however, RNA from the tumour cells can also be absorbed. Its detection in extracted RNA, therefore, can be used as a diagnostic tool.

Analysing blood samples in this way is known as conducting a liquid biopsy.

To test whether it worked, researchers led by Myron Best took blood samples from 700 people. The cohort included some with late-stage non-small cell lung cancer, some with early-stage cancer, others with a range of other conditions such as multiple sclerosis and pancreatitis, and some volunteers known to be cancer-free to act as controls.

The test, dubbed thromboSeq, utilised an algorithm. The researchers applied it to 5000 different RNA molecules found in platelets, having optimised it to continuously refine a key group that indicated the presence of cancer.

Having done so, they then applied it to the participant blood samples. The algorithm successfully identified lung cancer in 81% of cases.

The researchers concede that at present the results, while good, are not robust enough to recommend using thromboSeq as a stand-alone diagnostic test. However. Best suggests the findings are promising enough to warrant the start of clinical trials.

“Although the tumor-educated platelets blood test does not, so far, provide perfect predictions, it may complement alternative liquid biopsy bio-sources such as cell-free DNA, extracellular vesicles, circulating proteins, and circulating tumor cells as well as imaging modalities such as CT scans,” he says.