If cancer is detected at an early stage, the chances of recovery are greatest. Researchers have now found a new way of detecting changes in blood and urine that indicate a tumor in the body. To do this, they analyze what are known as glycosaminoglycans (GAGs), certain sugar compounds whose structure is altered by tumors. With a maximum of five percent false positive test results, up to 62.3 percent of cancers could be detected. From the researchers' point of view, the test could represent a simple and inexpensive way of early detection. Before it can be used clinically, however, it must prove itself in further studies.
The early detection of cancer has so far been based primarily on specific screening tests, including mammography and colonoscopy. In order to improve the early detection of various types of cancer, scientists are looking for so-called biomarkers - characteristics in blood or tissue samples that indicate certain processes in the body, for example the existence of a tumor. The most widely used approach to date is to look for circulating DNA fragments (cfDNA) of the tumor. However, some early-stage tumor types do not shed any DNA snippets at all into the blood, and the tests have so far been so complex and expensive that they are not very suitable for routine mass use.
Cancer-related changes
A team led by Sinisa Bratulic from Chalmers University of Technology in Gothenburg has now tested an alternative approach. Instead of circulating DNA, the researchers focused on so-called glycosaminoglycans (GAGs). These are sugar compounds that can be detected in blood and urine and whose number and structure are altered by tumors. "First of all, we noticed that patients with renal cell carcinoma had a significantly altered glycosaminoglycan profile in their blood and urine," the researchers report. "This led us to analyze the composition of glycosaminoglycans in other types of cancer."
To do this, Bratulic and his team examined blood and urine samples from 1,260 people with 14 different types of cancer and compared them with samples from healthy controls. With the help of machine learning, they worked out which patterns are typical for cancer diseases. They found changes that are specific to certain types of cancer as well as those that are common to all types of cancer examined.
Validation with blood bank
The researchers adjusted the test to a specificity of 95 percent. This means that it shows a false positive result in a maximum of five percent of healthy test persons. Under this condition, the sensitivity of the blood samples to early-stage cancer was 41.6 percent. In combination with a urine sample, the sensitivity increased to 62.3 percent. This means that around six out of ten cancer patients are correctly identified, four receive a false negative result. For comparison: The best tests based on cfDNA achieved a sensitivity of up to 70 percent in a study. However, these have not yet been externally validated. In a validation study, a test based on this principle only detected five out of 49 cancers, which corresponds to a sensitivity of around ten percent.
Bratulic and his team tested their method using samples from a Dutch blood bank. To do this, they selected 171 patients from samples from more than 145,000 people who had been diagnosed with cancer within 18 months of the blood collection. They compared these with samples from 110 healthy people. In this case, the test already recognized GAG cancer markers in the blood sample in 31 percent of the later cancer patients. If the researchers only looked at a subgroup of patients whose cancer was particularly severe, the sensitivity of the test was 43 percent. In addition, the researchers validated the results in a mouse model by implanting tumor cells in mice. The animals then also showed a correspondingly altered GAG profile.
Long way to clinical practice
With an estimated cost of around 50 euros per test, the new method would be significantly cheaper than cfDNA tests. From the authors' point of view, this could make it suitable for mass deployment. "However, before it can be used regularly, there would have to be extensive validation in large prospective studies," says Edgar Dahl from the University Hospital of RWTH Aachen University, who was not involved in the study. “Although the specificity of 95 percent sounds good at first, it would mean for a diagnostic screening test that every 20th patient (i.e. five percent) would be given a false positive; with one million people tested, this would be 50,000 people.”
One problem is that, in addition to tumors, other diseases can also lead to changes in the GAGs. These include, for example, inflammation in the body and the metabolic syndrome, which is associated with obesity, high blood pressure and disorders in fat and sugar metabolism. "Metabolic syndromes or certain inflammatory diseases are not uncommon, especially in old age," says Almut Schulze from the German Cancer Research Center in Heidelberg, who was also not involved in the study.
She also points out that the study population examined cannot be transferred one-to-one to other populations. "People in the US are probably generally sicker than the Dutch, which could lead to more false positives in the US," said Schulze. "Nevertheless, if the test works well with real-world data from different populations, it could sooner or later be included in the screening routine."
Source: Sinisa Bratulic (Chalmers University of Technology, Gothenburg, Sweden) et al., Proceedings of the National Academy of Sciences, doi: 10.1073/pnas.2115328119