Analysis of Therapeutic Targets and Prognostic Biomarkers Among semaphorins in the glioblastoma Microenvironment

Background: Glioblastoma (GBM) is the most invasive and common form among brain cancers in adults. GBM is characterized for its poor survival and markedly high tumors heterogeneity with shortage of effective therapies. Semaphorins, a family of membrane-associated and secreted proteins, were originally defined as neuronal growth pyramidal proteins involved in directing repulsive axons. Semaphorins are repeatedly involved in the evolution of neural circuits, involving not only the generation and guidance of neurons, but also the recognition of target regions and cells and synapse formation. However, the differential expression and clinical prognostic value of semaphorins in GBM were not yet available clarity. Methods In this study, various databases including ONCOMINE (1159 samples), GEPIA (TCGA and GTEx dataset), UALCAN (samples from TCGA dataset), cBioPortal (604 samples from GDAC firehose of TCGA dataset), GeneMANIA(data from publicly available daatbases, e.g. GEO, BioGRID) and TIMER(samples from TCGA) were exploited. Results We found that in GBM tissues the transcriptional levels of SEMA3A/3B/3E/3F/5A/6A were markedly elevated, while those of SEMA3G/4A/4D/4F/5B were markedly reduced. GBM patients with lower levels of SEMA3F/4F transcription had a significantly better outcome. The function of semaphorins was mainly related to the regulation of cell growth and development. Besides, we found that the expression of semaphorin was significantly correlated with the infiltration of immune cells. Conclusions Semaphroins are differentially expressed in glioblastoma compared with normal brain tissue. They could provide diverse prognostic values, participate in various molecular pathways. In addition, the semaphorin protein family plays an important role in immune cell infiltration. Our study may supply potential target genes for the treatment of glioblastoma while providing new insights into the selection of prognostic biomarkers. Besides, our results may offer new insights into immunotherapy targeting and analysis of protein co-expression in SEMA for glioblastoma.