Increased expression of HBXIP (LAMTOR5) predicts poor prognosis and is correlated with immune-cell infiltration in glioma.

IF 1.5 4区 医学 Q4 ONCOLOGY Translational cancer research Pub Date : 2024-11-30 Epub Date: 2024-11-27 DOI:10.21037/tcr-24-1982
Linyang Shi, Hui Chen, Junmin Chen, Joshua D Palmer, Lin Wang, Li Sheng
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Abstract

Background: The poor response of patients with gliomas to existing immunotherapy has resulted in negligible improvement in prognosis. It is widely acknowledged that HBXIP serves as a transcriptional activator implicated in tumorigenesis across various cancer types. However, its specific role within glioma remains unclear. The aim of this study was to determine the association between HBXIP expression and survival and tumor-infiltrating immune cells. In addition, to construct a prognostic model to predict the overall survival (OS) of patients with glioma.

Methods: Transcriptome sequencing data of 325 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 702 patients with glioma in The Cancer Genome Atlas (TCGA) were included for retrospective analysis and were used as the training group and the validation group, respectively. The expression of HBXIP in pancancer was detected in the database. A t-test and one-way analysis of variance were used to determine the differential expression levels of HBXIP across distinct subgroups of glioma. Functional annotations pertaining specifically to HBXIP's biological relevance underwent scrutiny via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The prognostic significance of HBXIP in glioma was ascertained through Kaplan-Meier curves and Cox regression models, a nomogram was used to establish a prognostic model, and the predictive power was evaluated with calibration curves and the concordance index. HBXIP's association with inhibitory immune checkpoints and tumor immune cell infiltration was examined using Pearson correlation coefficients via Tumor Immune Estimation Resource database.

Results: We found that HBXIP was upregulated in glioma, and that elevated HBXIP expression correlated significantly with adverse clinicopathological features and decreased OS. Multivariate analysis showed that HBXIP was an independent prognostic biomarker for glioma, and the established prognostic model could accurately predict the OS of patients. We also found that HBXIP expression was positively correlated with inhibitory immune checkpoint expression, HBXIP overexpression was associated with increased levels of tumor immunoinfiltrating cells in glioma that resulted in poor survival, and HBXIP demonstrated a positive correlation with the expression of immune cell marker genes.

Conclusions: HBXIP is closely related to the clinicopathologic factors in glioma and may function as an oncogene. Its high expression is associated with poor prognosis, which may potentially be linked to immune escape and immune cell infiltration. HBXIP is a potential biomarker of prognostic and immune infiltration in glioma.

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HBXIP (LAMTOR5)的表达增加预示着胶质瘤的不良预后,并与免疫细胞浸润相关。
背景:胶质瘤患者对现有免疫治疗的不良反应导致预后的改善微不足道。人们普遍认为,HBXIP是一种转录激活因子,与各种癌症类型的肿瘤发生有关。然而,其在胶质瘤中的具体作用尚不清楚。本研究的目的是确定HBXIP表达与生存和肿瘤浸润免疫细胞之间的关系。此外,构建预测胶质瘤患者总生存期(OS)的预后模型。方法:将中国胶质瘤基因组图谱(CGGA)数据库中325例胶质瘤患者的转录组测序数据和癌症基因组图谱(TCGA)中702例胶质瘤患者的转录组测序数据进行回顾性分析,分别作为训练组和验证组。在数据库中检测HBXIP在胰腺癌中的表达。采用t检验和单因素方差分析来确定HBXIP在胶质瘤不同亚组中的差异表达水平。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)分析,对HBXIP生物学相关性的功能注释进行了详细检查。通过Kaplan-Meier曲线和Cox回归模型确定HBXIP在胶质瘤中的预后意义,采用nomogram建立预后模型,并通过校准曲线和一致性指数评估预测能力。通过肿瘤免疫估计资源数据库使用Pearson相关系数检验HBXIP与抑制性免疫检查点和肿瘤免疫细胞浸润的相关性。结果:我们发现HBXIP在胶质瘤中表达上调,且HBXIP表达升高与不良临床病理特征及OS降低有显著相关性。多因素分析显示HBXIP是胶质瘤独立的预后生物标志物,建立的预后模型可以准确预测患者的OS。我们还发现HBXIP表达与抑制性免疫检查点表达呈正相关,HBXIP过表达与胶质瘤中肿瘤免疫浸润细胞水平升高相关,导致生存不良,HBXIP与免疫细胞标记基因表达呈正相关。结论:HBXIP与胶质瘤的临床病理因素密切相关,可能具有致癌基因的作用。其高表达与预后不良有关,可能与免疫逃逸和免疫细胞浸润有关。HBXIP是神经胶质瘤预后和免疫浸润的潜在生物标志物。
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来源期刊
CiteScore
2.10
自引率
0.00%
发文量
252
期刊介绍: Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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