A new method for early cancer detection may be the new future of "blood test for cancer"!

Many researchers, clinicians, and patients demand accurate and speedy detection of various tumors utilizing a non-invasive or minimally invasive technique. However, we did not previously have adequate technology to accomplish this. Because of cancer's subtle beginning and quick progression, many patients are frequently detected in the middle and late stages, missing the ideal treatment window, which often results in a huge financial burden and significant psychological stress for the patient's families.

In fact, the concept of early cancer screening through blood testing is not something that has only emerged in recent years. Just recently, Elizabeth Holmes, the founder of the American company Theranos, was sentenced to 135 months in prison for fraud for the "blood test for cancer" scam, and the blood test company, once valued at $9 billion, collapsed.

Early detection of physical anomalies in cancer patients will significantly increase survival rates and lessen the toll on families and society.

Although there are comparable detection techniques and gold standards for several common cancers, including breast, lung, and liver cancer, it is unfortunately challenging for the current mainstream detection techniques to accomplish accurate and quick screening for many types of early malignancies.

"Noninvasive detection of any-stage cancer using free glycosaminoglycans", a recent PNAS paper, reports on a novel, previously untested technology that may effectively identify multiple types of early-stage cancers concurrently, including cancers that were previously difficult to detect.

As early as 2021, a genomics-driven liquid biopsy (MCED) technology for early cancer detection was reported in a sub-publication of Science and Nature, which simply involves using a patient's blood sample to analyze the tumor components in their body fluids, including circulating tumor cells and cell-free structured tumor DNA, and then detecting the methylation of gene expression by DNA genome sequencing combines the blood test with machine learning and other techniques to look for abnormal methylation changes in the body and to predict where the cancer is located in the body. Test results are available within 10 business days after the sample arrives at the lab.

However, the technique described above is not flawless, and the sophisticated testing necessary for these advanced liquid biopsies raises the cost of measurement, making screening too expensive for the general public. More crucially, only a few liquid biopsies have been verified in an externally representative sample with MCED for stage I sensitivity.

In order to optimize the detection of early cancers in body fluids and to fill the information gap of the current liquid biopsy platform, this newly published approach investigates no longer genomics and proteomics, but cancer metabolism as an identifiable cancer marker. The discovery of glycosaminoglycan (GAG) biosynthesis with cancer-specific reprogramming through systems biology pan-cancer analysis of tumor metabolism in the authors' previous study, and the authors' finding of a significantly altered plasma and urine free GAGomes in renal cell carcinoma (RCC), prompted the authors to study free GAGomes in different cancer types and to develop a standardized high-throughput ultra performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) method to measure free GAGomes.

Given the presence of unique free GAGomes in different cancer types, the authors also explored whether these patterns could be used to identify cancer types and found that the predictive accuracy of using free GAGomes to predict putative cancer location (PCL) was 89.2%, while survival analysis showed that patients with undetectable free GAGome MCED scores had a better prognosis and less aggressive cancer phenotypes, and that it was not significantly associated with tumor stage and grade.

This work shows that the metabolic nature of free GAGomes, as well as their capacity to detect poor cfDNA shedding cancer types, may considerably supplement genomic biomarker-based liquid biopsies, opening the way for a multimodal MCED method. This method may boost sensitivity to stage I malignancies even more, to the point where cancer mortality can be significantly reduced by early identification alone.

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