Proteins could be biomarkers for glioma-related epilepsy: Study
Levels of 2 proteins linked to seizures, disease prognosis in patients
The LY6H and GRM3 proteins could serve as potential biomarkers of glioma-related epilepsy (GRE), according to a study.
Among people with gliomas, both proteins were found at lower levels in those who also had epilepsy relative to those who did not. The protein levels were also linked to disease prognosis and survival.
“This discovery not only provides new biomarkers for the early diagnosis of GRE but also offers significant insights into the molecular mechanisms underlying GRE and the development of novel therapeutic strategies,” the researchers wrote.
The study, “Identification and validation of LY6H and GRM3 as candidate biomarkers for Glioma-related epilepsy,” was published in Scientific Reports.
Gliomas are a class of tumors arising from glia, the support cells of the brain and spinal cord. People with gliomas commonly experience seizures — characterized by bursts of uncontrolled electrical activity in the brain — which is known as glioma-related epilepsy, or GRE.
Seizures and disease progression
About half of people with high-grade glioma, a faster-growing and more aggressive form, experience GRE. Up to 90% of those with low-grade glioma, which is slower growing, experience it, according to the authors.
GRE can be life-threatening and have substantial impacts on life quality. Recurrent seizures can also potentially speed disease progression, influencing prognosis and survival.
“Elucidating the molecular mechanisms underlying GRE is therefore crucial for accurate prognosis assessment and the development of effective treatment strategies,” the researchers wrote, though they noted that these mechanisms remain poorly understood.
The researchers focused on identifying proteins that may be involved in GRE. They examined brain tissue samples collected from people newly diagnosed with glioma — 20 with GRE and 10 without it — ages 18-70, who underwent surgery at a hospital in China.
Gliomas for all participants were diffuse, meaning having a propensity to spread, invading and mixing in with healthy tissue.
Protein analyses identified more than 1,000 proteins seen at different levels in people with or without epilepsy. Using various bioinformatics and artificial intelligence-based approaches, the scientists worked to hone in on which ones might play the most significant role in GRE.
Ultimately, the team identified two proteins — LY6H and GRM3 — that appeared most closely linked to GRE and had a high performance when distinguishing between people with and without the seizure disorder. Levels of both of these proteins were reduced in GRE compared with glioma without epilepsy.
The scientists validated their findings in a separate gene activity data set, finding that the genes encoding production of LY6H and GRM3 had significantly reduced activity in GRE. Activity of these genes again had a strong diagnostic performance for identifying GRE.
Further analyses indicated that activity of these genes decreased as the grade, or aggressiveness, of the tumor increased. Higher gene activity was also linked to better survival.
“This suggests the potential of LY6H and GRM3 as promising targets for glioma-specific therapies,” the researchers wrote.
The GRM3 protein, known as the metabotropic glutamate receptor 3, is found at synapses, the sites where nerve cells meet to communicate, where its activation inhibits the release of a brain signaling chemical called glutamate.
LY6H is also known to influence synaptic signaling, and has increasingly been found to play a role in cancer development.
Both have been previously linked to glioma and associated with glioma prognosis. Studies have also implicated both proteins in possible epilepsy-promoting processes, although their mechanisms in glioma-related epilepsy warrant further investigation, the researcher said.
“Although the exact pathways through which the reduced expression of LY6H and GRM3 triggers GRE remain unclear, our results sufficiently demonstrate the critical and significant roles of these two proteins in GRE,” they wrote.
Not only might these proteins eventually serve as treatment targets for both glioma progression and GRE, but they may also have diagnostic utility for identifying people at a high risk for GRE, according to the authors.
“Overall, LY6H and GRM3, with their excellent diagnostic performance and clinical feasibility, hold promise as essential tools for clinicians to promptly identify and manage GRE patients, thereby significantly improving patient outcomes and advancing precision medicine,” the researchers wrote.
They noted that larger studies will be needed to validate the findings and further examine the role of these proteins in GRE.
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