Abstract
IntroductionGlioblastoma (GBM) is the most lethal primary malignant brain tumor in adults with poor survival due to acquired therapeutic resistance and rapid recurrence. Currently, the standard clinical strategy for glioma includes maximum surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy; however, the median survival of patients with GBM remains poor despite these comprehensive therapies. Therefore, the identification of new prognostic biomarkers is urgently needed to evaluate the malignancy and long‐term outcome of glioma.AimsTo further investigate prognostic biomarkers and potential therapeutic targets for GBM.ResultsIn this study, we identified tribbles pseudokinase 2 (TRIB2) as one of the genes that is most correlated with pathological classification, radioresistance, and TMZ resistance in glioma. Additionally, the expression of mitogen‐activated protein kinase kinase kinase 1 (MAP3K1) showed a strong correlation with TRIB2. Moreover, a combined increase in TRIB2 and MAP3K1 was observed in GBM and indicated a poor prognosis of patients with glioma. Finally, enriched TRIB2 expression and MAP3K1 expression were shown to be associated with resistance to TMZ and radiotherapy.ConclusionCombined elevation of TRIB2 and MAP3K1 could be novel prognostic biomarkers and potential therapeutic targets to evaluate the malignancy and long‐term outcomes of GBM.
Highlights
Glioblastoma (GBM) is the most lethal primary malignant brain tumor in adults with poor survival due to acquired therapeutic resistance and rapid recur‐ rence
A combined increase in tribbles pseudokinase 2 (TRIB2) and MAP3K1 in glioma is associated with a poor prognosis and therapeutic resistance to TMZ and ra‐ diotherapy. These data suggest that TRIB2 and MAP3K1 could be used as novel therapeutic targets and prognostic biomarkers to evaluate the malignancy and long‐term outcome of GBM
Since TRIB2 was identified as an essential oncogene in a variety of cancer types, we focused on TRIB2 for further characterization of glioma in this study
Summary
Glioblastoma (GBM) is one of the most lethal and prevalent tu‐ mors in the adult central nervous system, with a morbidity of ap‐ proximately 7/10 000.1 Currently, the standard clinical strategy for glioma includes maximum surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy. Hou et al[7] found that TRIB2 increases colorectal cancer tumor growth by decreasing the expression of p21, which functions as a tumor suppressor gene, indicating that TRIB2 could become a potential molecular target for colorectal cancer. These studies prompted the hypothesis that TRIB2 is a prognostic predic‐ tor for multiple types of malignant tumors. A combined increase in TRIB2 and MAP3K1 in glioma is associated with a poor prognosis and therapeutic resistance to TMZ and ra‐ diotherapy These data suggest that TRIB2 and MAP3K1 could be used as novel therapeutic targets and prognostic biomarkers to evaluate the malignancy and long‐term outcome of GBM
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