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Glioma Marker Candidate Uncovered With Spatial Proteomics Approach

NEW YORK – By profiling blood samples collected in and around glioma tumors, a team led by investigators at Wuhan University has identified a blood proteomic signature for the cancer. The work appeared in Science Advances on Friday.

While the blood-brain barrier (BBB) largely buffers the brain from the widespread exchange of proteins with blood, glioma tumors can interfere with this barrier in places, the study's authors reasoned. Past research has actually pointed to more extensive protein exchange across the relatively permeable boundary between glioma tumors, vascular endothelial cells, and the blood in nearby arteries and draining veins, they noted.

"Our data offers a landscape view of the molecular changes induced by glioma, which may provide useful diagnostic and therapeutic clues in the ongoing battle against this deadly disease," senior and co-corresponding author Suming Chen, a researcher with Wuhan University's Institute for Advanced Studies, said in an email. "This innovative research strategy is also promising for application to mechanistic studies of other tumors."

For their analyses, Chen and his colleagues used an in situ sample collection strategy to assess spatially resolved samples at brain sites neighboring glioma tumors, bringing together magnetic resonance imaging and needle-based arterial and venous blood sampling during subsequent tumor resection surgeries.

"In the past, the study of tumors usually took tissues or peripheral blood for analysis," Chen explained. "In contrast, we collected blood from the feeding arteries and draining veins in the local environment of tumors."

Using this approach, along with liquid chromatography-mass spectrometry methods, the investigators profiled proteomic patterns in 19 blood samples from glioma arteries and 19 from draining veins, along with matched peripheral blood samples from foot veins in 18 participants. They also took a look at proteomic patterns in two dozen glioma tumor samples, five glioma perineural samples, and three normal brain tissue samples, as well as in peripheral blood samples for 71 individuals with or without glioma from two more research cohorts.

"The combined analysis of the proteomic results obtained from these interrelated multidimensional cohorts could not only discover glioma-specific proteins, but also provide deep insights into their genesis, migration, and exchange," the authors suggested.

Among other protein shifts, the team saw higher-than-usual expression of the mismatch repair protein PMS2P5 in blood from the glioma microenvironment and in peripheral blood samples from glioma patients, together with a dip in levels of the tumor suppressor protein CRTAC1.

The team also uncovered glioma-related blood plasma shifts in levels of SERPINA6 and other members of the serine proteinase inhibitor superfamily. In particular, SERPINA6 levels were significantly lower in peripheral blood samples from individuals with glioma, prompting follow-up analyses on its potential role as a glioma biomarker.

When they tested peripheral blood samples from 24 individuals with glioma and 25 glioma-free controls, the researchers found that SERPINA6 levels could distinguish between the two groups 89 percent of the time with a sensitivity of 87.5 percent and 88 percent specificity.

Such results suggested that blood plasma SERPINA6 levels "exhibited a high discriminative power and may serve as a biomarker of glioma," Chen suggested.

"[U]sing gliomas as an example, we have identified molecular features specific to gliomas through comparative tumor local environment-peripheral blood proteomics analysis and cross-validation," he said, noting that the "innovative spatial blood proteomics strategy" used in the study may also "provide a powerful means to reveal the mechanisms of tumorigenesis and development."