Abstract
Gliomas are the most common primary brain cancers. In recent years, IDH mutation and 1p/19q codeletion have been suggested as biomarkers for the diagnosis, treatment, and prognosis of gliomas. However, these biomarkers are only effective for a part of glioma patients, and thus more biomarkers are still emergently needed. Recently, an electrochemical communication between normal neurons and glioma cells by neuro-glioma synapse has been reported. Moreover, it was discovered that breast-to-brain metastasis tumor cells have pseudo synapses with neurons, and these synapses were indicated to promote tumor progression and metastasis. Based on the above observations, we first curated a panel of 17 synapse-related genes and then proposed a metric, synapse score to quantify the “stemness” for each sample of 12 glioma gene expression datasets from TCGA, CGGA, and GEO. Strikingly, synapse score showed excellent predictive ability for the prognosis, diagnosis, and grading of gliomas. Moreover, being compared with the two established biomarkers, IDH mutation and 1p/19q codeletion, synapse score demonstrated independent and better predictive performance. In conclusion, this study proposed a quantitative method, synapse score, as an efficient biomarker for monitoring gliomas.
Highlights
Brain and other nervous system cancers are estimated to take up 1.4% of new cancers but 2.9% of cancer deaths in 2019 (Brain and Other Nervous System Cancer, 2019)
Terms with top 10 smallest combined false discovery rates (FDRs) values, except “peripheral nervous system neuron development” (GO:0048935) as gliomas are located in the central nervous system, are used for subsequent analysis
In order to investigate whether synapse-related genes can be biomarkers for glioma patients, we first curated a list of glutamate receptor signaling pathway (GO) terms associated with synapse, neuron, neurotransmitter transport, glutamate receptor, or cell junction
Summary
Brain and other nervous system cancers are estimated to take up 1.4% of new cancers but 2.9% of cancer deaths in 2019 (Brain and Other Nervous System Cancer, 2019). Gliomas are the most frequent of these cancers, including astrocytoma (including glioblastoma), oligodendroglioma, ependymoma, oligoastrocytoma (mixed glioma), malignant glioma, not otherwise specified (NOS) glioma, and a few rare histologies (Ostrom et al, 2016). The World Health Organization (WHO) classified gliomas into grades I to IV and introduced biomarkers of IDH mutation and 1p/19q codeletion in the 2016 edition (Louis et al, 2007; Wesseling and Capper, 2018). Glioblastoma (WHO grade IV) accounts for about half of gliomas, with a median survival of less than 2 years (Gramatzki et al, 2016; Ostrom et al, 2016). Gliomas with lower grade have a diverse prognosis, either progressing to be as poor as glioblastoma or living more than 10 years after effective treatment (Ruda and Soffietti, 2017).
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