Glioma is the most common type of cancer in the central nervous system. Conventional histopathological classification falls short in capturing the complete pathological spectrum of these tumors. The study of Jiazhe Lin aimed to identify prognostic and diagnostic biomarkers of glioma through gene database exploration, in vitro experiments and studies in animal models.
We correlated transcriptome sequencing data with clinical prognostic information of glioma patients. Bioinformatics analysis of mRNA and lncRNA data identified several prognostic genes and their associated signaling pathways. Notably, L1CAM-related genes, such as NRG1 and CHL1, emerged as potential prognostic biomarkers for glioma. We demonstrated in cell experiments that L1CAM is involved in processes related to glioma progression. Next, we used PET imaging to examine L1CAM analogs [11C]trimebutine and 4-O-[11C]methylhonokiol as potential diagnostic markers in a rat glioma model. Although [11C]trimebutine could penetrate the blood-brain barrier, its tumor uptake was similar to healthy brain tissue, making difficult to distinguish the glioma in PET images.
However, [11C]trimebutine binds specifically to ยต-opioid receptors, suggesting it has potential as tracer for these receptors. The other L1CAM mimic, 4-O-[11C]methylhonokiol showed specific binding to cannabinoid receptor type 2. However, 4-O-[11C]methylhonokiol proved to be a substrate of the P-glycoprotein (P-gp) efflux pump, making tumor delineation in the brain challenging. Inhibition of P-gp with tariquidar improved brain uptake and glioma detection with PET, suggesting 4-O-[11C]methylhonokiol may be a suitable tracer to assess P-gp activity.
In summary, our study identified promising candidates for glioma biomarker and PET tracer discovery.
