Scientists have created a simple test that detects more than 10 types of cancer in the early stages, and it costs only $100
A new study suggests that a single test based on measuring metabolic markers in blood and urine samples could potentially help screen for several different types of cancer in a cost-effective way. MedicalNewsToday.
“Our study explored a new layer of information, molecules involved in cancer metabolism. This method made it possible to detect many types of cancer that were missed by previous methods, and a significant proportion of them were in the first stage. Cancer is a complex disease, so the more layers of information we can explore non-invasively, say through a blood test, the more likely we are to be able to catch more cancer at the earliest possible stage. This study could add an important piece of the puzzle to the early detection of multiple cancers,” said study author Dr. Francesco Gatto, a researcher at the Karolinska Institute in Sweden and founder of the biotech company Elypta.
The attractiveness of liquid biopsy
Cancer found early is easier to treat and is associated with a lower risk of mortality. Despite the benefits of community cancer screening and early detection of cancer, screening tests are only available for a few types of cancer, such as breast cancer and colorectal cancer.
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Tissue biopsy is currently the gold standard for cancer diagnosis, but repeat biopsies are a challenge due to their invasive nature. On the contrary, due to their non-invasive nature, liquid biopsies could be a promising alternative for cancer diagnosis and monitoring.
As tumor cells grow, they release DNA, proteins, and other metabolic by-products that can be found in blood and other body fluids. Fluid biopsy refers to the detection of circulating tumor cells or tumor cell products in body fluids.
In recent years, researchers have developed liquid biopsies that can simultaneously detect several different types of cancer with a single test. Estimates based on a modeling study indicate that cancer mortality among persons aged 50–79 years can be reduced by 26% by screening for early detection of multiple cancers.
A significant number of liquid biopsies developed to date are based on the detection of circulating DNA of tumor cells. However, genitourinary cancers such as bladder, prostate, kidney and brain cancers such as gliomas do not secrete DNA and cannot be detected based on circulating tumor DNA.
In addition, these tests have shown poor accuracy in detecting cancer at an early stage.
Several recent improvements, including the simultaneous assessment of circulating levels of tumor DNA and proteins, have helped improve diagnostic accuracy. But the high cost associated with these tests makes them less suitable for screening the general population.
Moreover, the accuracy of most experimental liquid biopsies for the early detection of multiple cancers has only been demonstrated in the study population, and it remains unknown whether these assays can accurately detect cancer in the general population.
The ability to correctly identify positive cases is measured in terms of sensitivity. One of the few studies examining the external validity of liquid biopsy for the detection of multiple cancers found a sensitivity of 10% in detecting stage 1 cancer.
In other words, these assays may require further optimization before they can be widely disseminated.
Identification of key cancer biomarkers
Metabolic changes are one of the hallmarks of cancer cells. Previous studies have shown definite changes in the profile of glycosaminoglycans, a class of carbohydrates that are present in most cancer cell lines.
Glycosaminoglycans are negatively charged polysaccharides composed of repeating disaccharide subunits.
The composition of glycosaminoglycans can differ in the type of disaccharide units and the number of sulfate groups that give these compounds a negative charge.
In their previous work, the scientists were also able to distinguish people with RCC from healthy people based on changes in the glycosaminoglycan profile in urine and plasma samples. To accurately quantify changes in the glycosaminoglycan profile in body fluids, they also developed a standardized analytical method.
In the present study, scientists examined the ability of the glycosaminoglycan profile of urine and plasma samples to serve as a biomarker for the early detection of several different types of cancer.
Testing for 14 types of cancer
During the initial phase of the study, scientists collected urine and plasma samples from 426 healthy people and 553 people with 14 different types of cancer, including breast cancer, colorectal cancer, non-small cell lung carcinoma, brain cancer, and cancer of the genitourinary system.
The researchers measured 39 traits or characteristics associated with glycosaminoglycan metabolism in each sample.
They found that some characteristics of glycosaminoglycans differ between cancer patients and healthy people.
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Using algorithms, the researchers came up with the minimum number of features present in these biofluids that could distinguish cancer patients from healthy people. They found that 14 features of glycosaminoglycans in plasma, urine, and combined plasma and urine samples, respectively, could distinguish cancer patients from healthy individuals.
The sensitivity of plasma, urine, and combined rates of early detection of multiple cancers was 41,6%, 62,3%, and 61,4%, respectively. In addition, these measures had the same sensitivity for different types of cancer and showed a slight increase in sensitivity as the cancer progressed. The researchers were also able to predict the likely location of the tumor with 89% accuracy based on combined plasma and urine glycosaminoglycan profiles.
These glycosaminoglycan profile scores have also been associated with more aggressive cancers.
Prospective test sensitivity
The researchers assessed the sensitivity of early detection rates for multiple cancers based on data from the same study sample that was used to develop the model for these rates.
They assessed the external validity of the test using a different sample of 281 people included in a large study.
Urine and plasma samples taken from these apparently healthy participants at baseline were used to determine rates of early detection of multiple cancers. Of the 281 people, 171 were diagnosed with cancer during the 18-month period between study enrollment and follow-up visit. Using this data, the researchers assessed the ability of multiple cancer detection rates to accurately predict subsequent cancer diagnosis.
In this sample, rates of early detection of multiple cancers based on the glycosaminoglycan profile had a sensitivity of 21% for stage 1 cancer. At the same time, the sensitivity for any type of cancer with a poor prognosis was 43%.
Can biomarkers detect cancer progression?
The researchers then induced kidney cancer in a mouse to test whether the changes in the glycosaminoglycan profile were actually caused by cancer progression.
Removal of the kidney on the seventh day after the introduction of tumor cells into the kidneys caused metastasis of the previously localized cancer.
The researchers found that as the cancer progressed, urinary and plasma glycosaminoglycan levels also gradually changed.
These results suggest that changes in the glycosaminoglycan profile were causally associated with cancer progression.
Step in the right direction
Dr. Gatto noted that evaluation of the glycosaminoglycan profile in a single blood or urine sample would cost about $50, and evaluation of both fluids would cost $100.
This is 5 to 10 times cheaper than estimates for other liquid biopsies. Thus, this assay can be used in conjunction with other liquid biopsies that measure levels of circulating tumor DNA to facilitate early detection of multiple cancers.
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Dr. Gatto said that "the study is a proof of concept - it was conducted on 1000 participants with 14 types of cancer."
“To one day become a screening test for multiple cancers, the evidence would have to come from much larger studies (100 participants) and the test itself would require very careful design to be mass-produced at the highest quality. There is still time, but the future of early detection of multiple cancers is getting closer every year,” he added.
“While this test is difficult to compare with other MCED assays, it is promising and includes brain tumors that are not covered by currently available tests. The authors also state that this approach will be 5 to 10 times cheaper than genomic versions. However, much work will be required to confirm the usefulness and cost-effectiveness of these new technologies in real-world settings compared to traditional screening approaches,” said Dr. Santosh Kesari, neuro-oncologist and director of neuro-oncology at Providence St. Johns Medical Center.
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