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一种基于基底膜基因表达与免疫浸润相关性的新型风险模型,用于预测垂体腺瘤的侵袭性。

A novel risk model based on the correlation between the expression of basement membrane genes and immune infiltration to predict the invasiveness of pituitary adenomas.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Department of Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

出版信息

Front Endocrinol (Lausanne). 2023 Jan 4;13:1079777. doi: 10.3389/fendo.2022.1079777. eCollection 2022.

Abstract

OBJECTIVE

Invasive pituitary adenomas (IPAs) are common tumors of the nervous system tumors for which invasive growth can lead to difficult total resection and a high recurrence rate. The basement membrane (BM) is a special type of extracellular matrix and plays an important role in the invasion of pituitary adenomas (PAs). The aim of this study was to develop a risk model for predicting the invasiveness of PAs by analyzing the correlation between the expression of BM genes and immune infiltration.

METHODS

Four datasets, featuring samples IPAs and non-invasive pituitary adenomas (NIPAs), were obtained from the Gene Expression Omnibus database (GEO). R software was then used to identify differentially expressed genes (DEGs) and analyze their functional enrichment. Protein-protein interaction (PPI) network was used to screen BM genes, which were analyzed for immune infiltration; this led to the generation of a risk model based on the correlation between the expression of BM genes and immunity. A calibration curve and receiver operating characteristic (ROC) curve were used to evaluate and validate the model. Subsequently, the differential expression levels of BM genes between IPA and NIPA samples collected in surgery were verified by Quantitative Polymerase Chain Reaction (qPCR) and the prediction model was further evaluated. Finally, based on our analysis, we recommend potential drug targets for the treatment of IPAs.

RESULTS

The merged dataset identified 248 DEGs that were mainly enriching in signal transduction, the extracellular matrix and channel activity. The PPI network identified 11 BM genes from the DEGs: and . Based on the complex correlation between these 11 genes and immune infiltration, a risk model was established to predict PAs invasiveness. Calibration curve and ROC curve analysis (area under the curve [AUC]: 0.7886194) confirmed the good predictive ability of the model. The consistency between the qPCR results and the bioinformatics results confirmed the reliability of data mining.

CONCLUSION

Using a variety of bioinformatics methods, we developed a novel risk model to predict the probability of PAs invasion based on the correlation between 11 BM genes and immune infiltration. These findings may facilitate closer surveillance and early diagnosis to prevent or treat IPAs in patients and improve the clinical awareness of patients at high risk of IPAs.

摘要

目的

侵袭性垂体腺瘤(IPA)是常见的神经系统肿瘤,其侵袭性生长可导致难以完全切除和高复发率。基底膜(BM)是一种特殊类型的细胞外基质,在垂体腺瘤(PAs)的侵袭中起着重要作用。本研究旨在通过分析 BM 基因表达与免疫浸润的相关性,建立预测 PAs 侵袭性的风险模型。

方法

从基因表达综合数据库(GEO)中获取四个包含 IPA 和非侵袭性垂体腺瘤(NIPA)样本的数据集。使用 R 软件识别差异表达基因(DEGs)并分析其功能富集。蛋白质-蛋白质相互作用(PPI)网络用于筛选 BM 基因,并分析其免疫浸润情况;由此生成了一个基于 BM 基因表达与免疫相关性的风险模型。使用校准曲线和接收者操作特征(ROC)曲线对模型进行评估和验证。随后,通过定量聚合酶链反应(qPCR)验证手术中 IPA 和 NIPA 样本之间 BM 基因的差异表达水平,并进一步评估预测模型。最后,基于我们的分析,为 IPA 的治疗推荐了潜在的药物靶点。

结果

合并数据集鉴定出 248 个主要富集在信号转导、细胞外基质和通道活性中的 DEGs。PPI 网络从 DEGs 中鉴定出 11 个 BM 基因:和。基于这 11 个基因与免疫浸润之间的复杂相关性,建立了一个预测 PAs 侵袭性的风险模型。校准曲线和 ROC 曲线分析(曲线下面积[AUC]:0.7886194)证实了该模型的良好预测能力。qPCR 结果与生物信息学结果的一致性证实了数据挖掘的可靠性。

结论

使用多种生物信息学方法,我们建立了一种新的风险模型,基于 11 个 BM 基因与免疫浸润的相关性来预测 PAs 侵袭的概率。这些发现可能有助于更密切的监测和早期诊断,以预防或治疗患者的 IPA,并提高高危 IPA 患者的临床意识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/280c/9846255/73c8519b2b7c/fendo-13-1079777-g001.jpg

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