IKBIP可能成为胶质母细胞瘤的一个潜在预后生物标志物。
IKBIP might be a potential prognostic biomarker for glioblastoma multiforme.
发表日期:2023 Mar 27
作者:
Hong Chen, Bo Liang, Xiaolin Luo, Wenyu Zhang, Xiong Song, Hailin Lan, Qiuyuan Yue, Jingdun Xie, Mingwei Zhang
来源:
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要:
由于抑制核因子-kB激酶相互作用蛋白(IKBIP)与胶质瘤患者的生存率负相关,本研究旨在全面分析IKBIP在多形性胶质母细胞瘤(GBM)中的潜在功能。GBM样本从The Cancer Genome Atlas和中国胶质瘤基因组图谱中分别检索作为训练和验证队列,并进行生存和Cox回归分析。基于临床指标和IKBIP,建立了三个预测模型,然后使用验证数据集进行验证。还进行了浸润免疫细胞分析和单样本基因集富集分析以探索潜在机制。最后,通过分子生物学实验证实了关键发现。高IKBIP评分组患者的生存率较差。基于Cox回归和亚组分析,确定IKBIP是独立的预后因素。在构建的三个模型中,将IKBIP签名和临床特征组合的模型在训练队列中表现良好,并具有区分度、校准和模型改进能力。这个模型在CGGA的外部队列中也得到了成功验证。进一步分析表明,许多免疫细胞和相关通路都涉及高风险组。体外实验表明,IKBIP的敲除抑制了细胞浸润和增殖,并促进了它们的衰老。鉴定了IKBIP的预测价值及其对GBM浸润性的积极影响,表明IKBIP可能作为GBM治疗的潜在靶点。 版权所有©2023 Elsevier B.V.。
Due to the negative association between inhibitor of nuclear factor-kB kinase-interacting protein (IKBIP) and survival in gliomas, this study aimed to comprehensively analyze the potential function of IKBIP in glioblastoma multiforme (GBM).GBM samples were retrieved from The Cancer Genome Atlas and Chinese Glioma Genome Atlas as training and validation cohorts, respectively, and survival and Cox regression analyses were conducted. Based on clinical indicators and IKBIP, three prognostic models were established and then verified using the validation dataset. Infiltrating immune cell analysis and single-sample gene set enrichment analysis were also conducted to explore the underlying mechanisms. Finally, the key findings were validated through molecular biology experiments.Patients in the high IKBIP score group had poorer survival. Based on Cox regression and subgroup analyses, IKBIP was identified as an independent prognostic factor. Among the three models constructed, the model combining the IKBIP signature and clinical features displayed good performance in terms of discrimination, calibration, and model improvement capability in the training cohort. This model was also successfully validated in an external cohort from the CGGA. Further analysis revealed that many immune cells and related pathways were involved in the high-risk group. In vitro experiments revealed that the knockdown of IKBIP inhibited cell invasion and proliferation, and promoted their senescence.The prognostic value of IKBIP and its positive impact on the invasiveness of GBM were identified, indicating that IKBIP may serve as an underlying target for the treatment of GBM.Copyright © 2023 Elsevier B.V. All rights reserved.