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Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma.
CNS Neuroscience & Therapeutics ( IF 4.8 ) Pub Date : 2019-07-18 , DOI: 10.1111/cns.13197
Jia Wang 1, 2 , Jie Zuo 3 , Alafate Wahafu 1 , Mao-de Wang 1, 2 , Rui-Chun Li 1 , Wan-Fu Xie 1
Affiliation  

INTRODUCTION Glioblastoma (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. AIMS To further investigate prognostic biomarkers and potential therapeutic targets for GBM. RESULTS In 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. CONCLUSION Combined elevation of TRIB2 and MAP3K1 could be novel prognostic biomarkers and potential therapeutic targets to evaluate the malignancy and long-term outcomes of GBM.

中文翻译:

TRIB2和MAP3K1的联合升高提示胶质母细胞瘤的替莫唑胺预后不良和化学耐药性。

简介胶质母细胞瘤(GBM)是成人中最致命的原发性恶性脑肿瘤,由于获得性治疗抗性和快速复发,生存期较差。目前,神经胶质瘤的标准临床策略包括最大程度的手术切除,放疗和替莫唑胺(TMZ)化疗。然而,尽管采取了这些综合疗法,GBM患者的中位生存率仍然很差。因此,迫切需要鉴定新的预后生物标志物以评估神经胶质瘤的恶性程度和长期预后。目的进一步研究GBM的预后生物标志物和潜在治疗靶标。结果在这项研究中,我们确定了Tribbles假激酶2(TRIB2)是与神经胶质瘤的病理学分类,放射抵抗和TMZ耐药性最相关的基因之一。此外,丝裂原活化蛋白激酶激酶激酶1(MAP3K1)的表达与TRIB2密切相关。此外,在GBM中观察到TRIB2和MAP3K1的联合增加,表明神经胶质瘤患者的预后较差。最后,富集的TRIB2表达和MAP3K1表达与对TMZ和放射疗法的耐药性相关。结论TRIB2和MAP3K1联合升高可能是评估GBM恶性和长期预后的新的预后生物标志物和潜在的治疗靶标。富含TRIB2表达和MAP3K1表达被证明与TMZ和放疗耐药有关。结论TRIB2和MAP3K1联合升高可能是评估GBM恶性和长期预后的新的预后生物标志物和潜在的治疗靶标。富集的TRIB2表达和MAP3K1表达被证明与TMZ和放疗耐药有关。结论TRIB2和MAP3K1联合升高可能是评估GBM恶性和长期预后的新的预后生物标志物和潜在的治疗靶标。
更新日期:2019-11-18
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