So far, many cancers are only discovered when noticeable symptoms appear or tumors are recognizable. However, a blood test could help detect cancer in the body in the future. In a study with more than 6,600 patients, researchers have now tested such a blood test that can display 50 types of cancer at once. It detects characteristic deposits on the genome of degenerate cells, which also circulates in fragments in the blood. Combined with a computer-aided evaluation, the test can recognize and assign these epigenetic markers. In the study, the false positive rate was only 0.7 percent, and the rate of correctly diagnosed cancer varied between 18 and 93 percent depending on the stage.
In the case of cancer, it depends on how early the tumors are recognized. Because the earlier the stage, the lower the risk that the cancer has already spread. Ideally, in very early stages of cancer, surgical removal of the tumor is sometimes sufficient without the need for stressful chemotherapy. The efforts of medicine to apply and develop meaningful early detection methods are correspondingly great. Some types of cancer, such as colon cancer or breast cancer, use procedures such as mammography or colonoscopy. However, suitable tests have so far been lacking for many other types of cancer. This is one of the reasons why scientists have been looking for a way to identify cancer through blood tests for a long time. These are based on the knowledge that there are some biomarkers and even cancer cells that circulate freely in the blood that can indicate a tumor disease.
Search for characteristic DNA attachments
A particularly promising approach is tests that do not look for typical DNA sequences of degenerate cells, but for epigenetic changes. These are small chemical groups, so-called methyl groups, which are located at different places in the genome. Where these attachments are located, the genes located at this point cannot be read, they are virtually switched off. Removing these attachments turns on previously blocked genes. Such epigenetic changes can, for example, activate tumor genes or switch off control genes against degeneration. Several research groups are already working on blood tests to detect various types of cancer using such epigenetic markers. The first studies included a test that could detect breast cancer, prostate and colon cancer and lymphoma.
Researchers from the Circulating Cell-free Genome Atlas (CCGA) consortium, led by Michael Seiden of US Oncology Research, have now developed this test procedure further. To do this, they created an assay that detects methyl group attachments at more than one million sites in DNA. The evaluation of this data is then carried out by a learning algorithm that has been trained to recognize the characteristic methylation patterns of 50 different types of cancer. The blood samples from 1,531 cancer patients and 1,521 healthy control persons served as training material in the training. The scientists then carried out the actual study with the blood samples from 1264 other participants. “To our knowledge, this is the most extensive clinical genomics program to date, in which a blood test for the early detection of numerous types of cancer has been developed and validated,” said Seiden and his team.
Hit rate between 18 and 93 percent
The study found that the blood test was successful in distinguishing cancer patients from healthy participants in the majority of cases and was also able to determine the type of cancer with high specificity, as the researchers report. According to this, the rate of false positive results was only 0.7 percent – in contrast, mammography series screenings for breast cancer can reach up to ten percent. In the blood test, however, the rate of successfully detected tumor diseases was significantly lower. Depending on the stage, the range for all 50 types of cancer ranged from an average of only 18 percent for very early tumors in stage I to 93 percent for advanced cancers (stage IV). The hit rate was 43.9 percent across all stadiums. The results were slightly better when the system only searched for the twelve most common cancers, including stomach cancer, colon cancer, lung cancer, liver cancer, and pancreatic cancer and leukemia. For these types of cancer, the blood test achieved a detection rate of 67.3 percent averaged over all stages.
In addition to recognizing whether the patient has cancer or not, the blood test and the algorithm used for the evaluation were also able to determine in which tissue or organ the degenerated cells are located. This was achieved in 96 percent of the samples tested positive. The error rate was around seven percent. Taken together, these results support the ability of this methylation test to meet the basic requirements of a multiple cancer screening blood test, ”says Seiden. This includes the detection of numerous types of cancer with just one test and a low false positive rate, but also the ability to indicate where the cancer is located in the body. The editor-in-chief of the specialist magazine Annals of Oncology, in which the study has now been published, is of a similarly positive opinion: “This is an important study and a first step towards the development of easy-to-use screening tools”, comments Fabrice André. “Even the early detection of more than 50 percent of cancer cases could save millions of lives worldwide every year.” However, further studies have yet to show whether the epigenetic tests are actually suitable for detecting tumors early enough. It will therefore take some time before such a blood test can be launched.
Source: Circulating Cell-free Genome Atlas (CCGA) consortium; Annals of Oncology, doi: 10.1016 / j.annonc.2020.02.011