Extracellular Phosphoproteins Could Lead To Cancer Blood Test

A series of of proteins in blood plasma have been identified that, when elevated, signify the presence of cancer. The findings mean doctors may soon be able to detect and monitor cancer with a simple blood test, reducing or eliminating the need for more invasive procedures.

While the work, that relies on analysis of microvesicles and exosomes in blood plasma, involved samples from breast cancer patients, researchers say it’s possible the method could work for any type of cancer and other types of diseases.

W. Andy Tao, a professor of biochemistry and member of the Purdue University Center for Cancer Research, says:

“There are so many types of cancer, even multiple forms for different types of cancer, that finding biomarkers has been discouraging. This is definitely a breakthrough, showing the feasibility of using phosphoproteins in blood for detecting and monitoring diseases.”

Phosphoproteins

Protein phosphorylation, the addition of a phosphate group to a protein can lead to cancer cell formation. So phosphorylated proteins, known as phosphoproteins, have been seen as prime candidates for cancer biomarkers.

Until now, however, scientists weren’t sure identification of phosphoproteins in blood was possible because the liver releases phosphatase into the bloodstream, which dephosphorylates proteins.

Researchers found nearly 2,400 phosphoproteins in a blood sample and identified 144 that were significantly elevated in cancer patients. Researchers compared 1-milliliter blood samples from 30 breast cancer patients with six healthy controls.

The researchers used centrifuges to separate plasma from red blood cells, and high-speed and ultra-high-speed centrifuges to further separate microvesicles and exosomes.

Those particles, which are released from cells and enter the bloodstream, may play a role in intercellular communication and are thought to be involved in metastasis, spreading cancer from one place to another in the body. They also encapsulate phosphoproteins, which Tao’s team identified using mass spectrometry.

Extracellular Vesicles

A simple blood test for cancer would be far less invasive than scopes or biopsies that remove tissue. A doctor could also regularly test a cancer patient’s blood to understand the effectiveness of treatment and monitor patients after treatment to see if the cancer is returning.

“Extracellular vesicles, which include exosomes and microvesicles, are membrane-encapsulated. They are stable, which is important,’ Tao says. “The samples we used were five years old, and we were still able to identify phosphoproteins, suggesting this is a viable method for identifying disease biomarkers. There is currently almost no way to monitor patients after treatment. Doctors have to wait until cancer comes back.”

The findings are promising for early detection of cancer, says Timothy Ratliff, director of the Purdue University Center for Cancer Research.

“The vesicles and exosomes are present and released by all cancers, so it could be that there are general patterns for cancer tissues, but it’s more likely that Andy will develop patterns associated with different cancers. It’s really exciting. Early detection in cancer is key and has been shown to clearly reduce the death rate associated with the disease.”

Tao next plans to analyze increased levels of phosphoproteins in various types of cancer to determine whether there are patterns that would signify the type of cancer a patient has. His company, Tymora Analytical, is also developing technology that would allow doctors to insert blood samples onto a cartridge and analyze phosphoproteins present, eliminating the need for ultra-high-speed centrifuges that aren’t practical in clinical settings.

The study was funded by the National Institutes of Health, the National Science Foundation, and the Purdue University Center for Cancer Research.

I-Hsuan Chen, Liang Xue, Chuan-Chih Hsu, Juan Sebastian Paez Paez, Li Pan, Hillary Andaluz, Michael K. Wendt, Anton B. Iliuk, Jian-Kang Zhu, and W. Andy Tao
Phosphoproteins in extracellular vesicles as candidate markers for breast cancer
PNAS 2017, doi:10.1073/pnas.1618088114

Image: Wheeler Cowperthwaite CC-BY

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