GENES ENCODING CELL SURFACE RECEPTORS AS NOVEL PROGNOSIS BIOMARKERS IN BRAIN TUMORS Free

A number of cell surface receptors that bind growth factors, neurotransmitters, and hormones are known to influence cancer initiation and progression. For example, CD114 (also called GCSFR or CSFR), which is encoded by the CSF3R gene, is a receptor for the granulocyte colony stimulating factor (GCSF) and a marker of cancer stem cells expressed in various cancer types. Also, the γ-aminobutyric acid (GABA) type A (GABAA) receptor for the inhibitory neurotransmitter GABA is proposed to play a role in brain cancer. Here, we report how the mRNA expression levels of CSF3R, the gene that encodes CD114, and genes encoding subunits of the GABAA receptor, are related to prognosis of brain tumor patients assessed by overall survival (OS).

Data were obtained from brain tumor datasets, mainly the French and The Cancer Genome Atlas (TCGA) datasets for gliomas and the Cavalli dataset for medulloblastoma. Gene expression was analyzed using the R2 Genomics Analysis and Visualization Platform. OS was calculated using the Kaplan-Meier estimate.

Levels of CSF3R⁄CD114 transcripts are higher in different types of gliomas, namely astrocytoma, pilocytic astrocytoma, and glioblastoma (GBM), in comparison to non-tumoral neural tissue. Higher expression of CSF3R in gliomas is associated with poorer outcome indicated by a shorter OS. Genes for GABAA receptor subunits associated with OS in gliomas include GABRA2, GABRA3, GABRG1, GABRG2, and GABRB3. Higher GABRA5 expression was associated with shorter patient OS in Group 3 and Group 4 medulloblastoma.

These findings indicate that gene expression levels of CSF3R and GABAA receptor subunits are potential biomarkers of poorer prognosis in patients with brain tumors.