Mining database for the therapeutic targets and prognostic biomarkers among STAT family in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with a high mortality rate. Aberrant activation of signal transducers and activators of transcription (STAT) signaling results in tumor pathogenesis and progression by regulating cell cycle, cell survival and immune response. METHODS: Therapeutic targets and prognostic biomarkers within the STAT family in GBM were explored using web applications and databases. RESULTS: High levels of STAT1/3/5A/5B/6 and low levels of STAT4 were observed in GBM patients. GBM patients expressing high STAT1/2/3/5A/6 and low STAT4/5B levels had the worse overall survival. Among the STAT family, STAT4 and STAT6 were the most frequently mutated genes. A low to moderate correlation among members of the STAT family was observed. Additionally, the STATs were involved in activation or inhibition of cancer related pathways. Analysis of immune infiltrates showed STAT5A levels to be significantly correlated with abundance of immune cells and levels of immune gene biomarkers. Gene ontology (GO) functions and KEGG pathway analysis indicated that STAT5A is involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway. Moreover, several kinase and transcription factor targets of STAT5A in GBM were identified. CONCLUSION: We report here therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM. These findings lay a foundation for further studies on the role of STAT family in therapy and prognosis of GBM. Further studies are required to verify our results.

Expression and clinical significance of CXC chemokines in the glioblastoma microenvironment.

BACKGROUND: Glioblastoma (GBM) is the most common subtype of brain cancer, encompassing 16% of all primary brain cancers. The prognosis of GBM is poor, with a 5-year-survial of approximately 5%. Increasing evidence has revealed that chemokines in the tumor microenvironment (TME) are often altered, thus affecting tumor proliferation and metastasis. METHOD: Multi-omics and bioinformatics tools were utilized to clarify the role of CXC chemokine in GBM. RESULT: Most CXC chemokines were found to be differentially regulated in GBM, which correlated with patient prognosis. CXC chemokines were found to activate cancer-related signaling pathways, thus affecting immune infiltration. Interestingly, this was found to be associated with drug resistance. Most CXC chemokines were significantly correlated with abundance of B cells, CD8+ cells and dendritic cells. Furthermore, somatic copy number alterations of CXC chemokines can inhibit dendritic cell infiltration. Moreover, CXCL1 was selected as a hub gene, and several kinase, miRNA and transcription factor targets of CXCL1 were identified. CONCLUSION: our study provides novel insights into CXC chemokine expression and their role in the GBM microenvironment. These results are able to provide more data about prognostic biomarkers and therapeutic targets of GBM.