TRAF3IP3 水平高预示着胶质瘤患者预后不良。

High TRAF3IP3 Level Predicts Poor Prognosis of Patients with Gliomas.

机构信息

Department of Oncology, The First People's Hospital of Chenzhou, Xiangnan University, Chenzhou, China.

出版信息

World Neurosurg. 2021 Apr;148:e436-e449. doi: 10.1016/j.wneu.2021.01.006. Epub 2021 Jan 12.

DOI:10.1016/j.wneu.2021.01.006

PMID:33444836

Abstract

BACKGROUND

Tumor necrosis factor receptor-related factor 3 (TRAF3) interacting protein 3 (TRAF3IP3) is involved in the development of immune tissues and the immune response of the body. Downregulated expression of TRAF3IP3 in malignant melanoma can inhibit tumor growth. The role of TRAF3IP3 in glioma is unknown.

METHODS

We used the Wilcoxon rank sum test to compare the expression of TRAF3IP3 in glioma and normal tissues based on The Cancer Genome Atlas and Genotype Tissue Expression. Logistics regression was used to evaluate the relationship between TRAF3IP3 and clinicopathologic characters. Gene set enrichment analysis and single-sample gene set enrichment analysis were conducted to annotate biological function of TRAF3IP3. We used Kaplan-Meier and Cox regression to evaluate the prognostic value of TRAF3IP3.

RESULTS

We downloaded RNA-seq data of 670 gliomas and 1157 normal tissues. TRAF3IP3 was highly expressed in gliomas (P < 0.001). High expression of TRAF3IP3 and higher World Health Organization grade (odds ratio [OR], 3.57 [2.42-5.34 CI]; P < 0.001), wild-type isocitrate dehydrogenase status (OR, 4.79 [3.40-6.83 CI]; P < 0.001), 1p/19q non-codeletion (OR, 15.32 [9.23-27.01 CI]; P < 0.001), mutant epidermal growth factor receptor status (OR, 2.77 [1.65-4.81 CI]; P < 0.001), worse histologic type (OR, 3.64 [2.48-5.43 CI]; P < 0.001) and worse primary therapy outcome (OR, 2.29 [1.47-3.61 CI]; P < 0.001) were significantly correlated. Six signaling pathways were significantly enriched in the TRAF3IP3 high-expression phenotype group, including JAK-STAT, interferon-γ, apoptosis, P53, programmed cell death protein 1, and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4). High expression of TRAF3IP3 was associated with worse progression-free survival (hazard ratio [HR], 2.39 (1.39-3.01); P < 0.001), disease-free survival (HR, 3.02 (2.27-4.01); P < 0.001) and overall survival (HR, 2.87 (2.20-3.75); P < 0.001).

CONCLUSIONS

TRAF3IP3 play an important role in the occurrence and development of glioma and may be a potential biomarker for the prognosis of glioma.

摘要

背景

肿瘤坏死因子受体相关因子 3（TRAF3）相互作用蛋白 3（TRAF3IP3）参与免疫组织的发育和机体的免疫反应。恶性黑色素瘤中 TRAF3IP3 的表达下调可抑制肿瘤生长。TRAF3IP3 在神经胶质瘤中的作用尚不清楚。

方法

我们基于癌症基因组图谱（The Cancer Genome Atlas）和基因型组织表达（Genotype Tissue Expression），使用 Wilcoxon 秩和检验比较了神经胶质瘤和正常组织中 TRAF3IP3 的表达。使用逻辑回归评估 TRAF3IP3 与临床病理特征的关系。进行基因集富集分析和单样本基因集富集分析以注释 TRAF3IP3 的生物学功能。我们使用 Kaplan-Meier 和 Cox 回归评估 TRAF3IP3 的预后价值。

结果

我们下载了 670 例神经胶质瘤和 1157 例正常组织的 RNA-seq 数据。TRAF3IP3 在神经胶质瘤中高表达（P<0.001）。TRAF3IP3 高表达和更高的世界卫生组织（World Health Organization）分级（比值比[OR]，3.57[2.42-5.34 置信区间（CI）]；P<0.001）、野生型异柠檬酸脱氢酶状态（OR，4.79[3.40-6.83 CI]；P<0.001）、1p/19q 非缺失（OR，15.32[9.23-27.01 CI]；P<0.001）、突变型表皮生长因子受体状态（OR，2.77[1.65-4.81 CI]；P<0.001）、较差的组织学类型（OR，3.64[2.48-5.43 CI]；P<0.001）和较差的一线治疗结局（OR，2.29[1.47-3.61 CI]；P<0.001）显著相关。TRAF3IP3 高表达表型组中显著富集了 6 条信号通路，包括 JAK-STAT、干扰素-γ、细胞凋亡、P53、程序性细胞死亡蛋白 1 和 CTLA-4（细胞毒性 T 淋巴细胞相关蛋白 4）。TRAF3IP3 高表达与无进展生存期（危险比[HR]，2.39[1.39-3.01]；P<0.001）、无病生存期（HR，3.02[2.27-4.01]；P<0.001）和总生存期（HR，2.87[2.20-3.75]；P<0.001）的降低显著相关。