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TRIB2 和 MAP3K1 的联合升高提示胶质母细胞瘤对替莫唑胺的预后不良和化疗耐药。

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Center of Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

CNS Neurosci Ther. 2020 Mar;26(3):297-308. doi: 10.1111/cns.13197. Epub 2019 Jul 18.

DOI:10.1111/cns.13197
PMID:31318172
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7053231/
Abstract

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.

摘要

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，由于获得性治疗耐药和快速复发，患者的生存率较差。目前，胶质瘤的标准临床策略包括最大限度的手术切除、放疗和替莫唑胺（TMZ）化疗；然而，尽管采用了这些综合疗法，GBM 患者的中位生存期仍然很差。因此，迫切需要识别新的预后生物标志物，以评估胶质瘤的恶性程度和长期预后。

目的

进一步研究胶质母细胞瘤的预后生物标志物和潜在治疗靶点。

结果

在这项研究中，我们确定了原癌基因丝氨酸/苏氨酸激酶 2（TRIB2）是与胶质瘤的病理分类、放射耐药性和 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 呈强烈相关性。此外，在 GBM 中观察到 TRIB2 和 MAP3K1 的联合增加，并提示胶质瘤患者的预后不良。最后，TRIB2 表达和 MAP3K1 表达的富集与 TMZ 和放疗耐药性相关。

结论

TRIB2 和 MAP3K1 的联合升高可能是评估 GBM 恶性程度和长期预后的新的预后生物标志物和潜在治疗靶点。

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