研究动态
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通过综合分析和机器学习鉴定与系统性红斑狼疮相关的乳腺癌预后基因。

Identification of prognostic genes for breast cancer related to systemic lupus erythematosus by integrated analysis and machine learning.

发表日期:2023 Aug 10
作者: Xiaofeng Liang, Zhishen Peng, Zien Lin, Xiaobing Lin, Weiyi Lin, Ying Deng, Shujun Yang, Shanshan Wei
来源: Cellular & Molecular Immunology

摘要:

系统性红斑狼疮(SLE)是一种自身免疫性疾病,涉及多个器官,一些研究发现SLE患者患乳腺癌(BRCA)的风险降低。因此,我们尝试通过整合分析和机器学习找出与SLE相关的BRCA预后基因。首先,我们从基因表达在线数据库(GEO)下载了2个SLE数据集和癌症基因组图谱(TCGA)的BRCA数据。随后,我们利用Metascape在SLE中进行了差异表达基因(DEGs)和功能富集分析。在两个数据集中差异表达的基因是经过验证的DEGs。在构建蛋白质相互作用(PPI)网络后,节点数大于30的基因与BRCA中的生存基因相交,得到候选基因。然后,在训练集和验证集中利用Lasso回归验证了这些候选基因,得到了预后基因。之后,我们研究了预后基因对SLE的诊断潜力和BRCA预后的预测效能。此外,对SLE和BRCA进行了基因集富集分析(GSEA)和免疫浸润分析。最后,我们构建了一个预后基因-miRNA网络,并对共同基因进行了功能富集分析。 SLE的DEGs主要富集于中性粒细胞脱颗粒化和干扰素(IFN)通路。在建立BRCA的Lasso模型后,确定了IRF7、IFI35和EIF2AK2作为与SLE相关的BRCA预后基因,并且对BRCA的预后有良好的预测能力。预后基因对SLE的诊断潜力较高,IFI35和EIF2AK2与SLE活动呈正相关,而IRF7与IFI35呈正相关。GSEA显示SLE和BRCA都与泛素化降解有关。免疫浸润分析表明SLE患者血浆细胞、树突状细胞(DC)、中性粒细胞和单核细胞升高。BRCA低风险组中DC、NK和CD8+ T细胞升高。最后,我们确认了5种共同的miRNAs,主要富集在IFN通路中。 IRF7、IFI35和EIF2AK2被确定为与SLE相关的BRCA预后基因。IFN通路在SLE的发病机制和BRCA的预后中起到重要作用。 © 2023 Elsevier GmbH。保留所有权利。
Systemic Lupus Erythematosus (SLE) is an autoimmune disease with multi-organ involvement, and some studies have found that SLE has a reduced risk of breast cancer (BRCA). So, we tried to find prognostic genes for BRCA related to SLE by integrated analysis and machine learning.First, we downloaded 2 SLE datasets from Gene Expression Omnibus (GEO) and BRCA data from the Cancer Genome Atlas (TCGA). Subsequently, we performed differentially expressed genes (DEGs) and functional enrichment analysis by Metascape in SLE. Genes that were differentially expressed in both datasets were the validated DEGs. And after constructing PPI network, genes with nodes >30 were intersected with survival genes in BRCA to obtain candidate genes. Then, the candidate genes were validated by lasso regression in both training and validation sets to obtain prognostic genes. Afterwards, we investigated the diagnostic potential of prognostic genes for SLE and the predictive efficacy for BRCA prognosis. Moreover, GSEA analysis and immune infiltration were performed for SLE and BRCA. Finally, we constructed a prognostic gene-miRNAs network and did functional enrichment of the shared genes.DEGs for SLE were mainly enriched with neutrophil degranulation and IFN pathways. After the lasso model of BRCA was established, IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE and had good predictive ability for the prognosis of BRCA. Prognostic genes had excellent diagnostic potential for SLE, with IFI35 and EIF2AK2 positively associated with SLE activity and IRF7 positively associated with IFI35. GSEA showed that both SLE and BRCA were associated with ubiquitinated degradation. Immune infiltrates suggest that plasma cells, dendritic cells (DC), neutrophils and monocyte were elevated in SLE. DC, NK and CD8+ T cells were elevated in the BRCA low-risk group. Finally, 5 shared miRNAs were confirmed, which were mainly enriched in the IFN pathway.IRF7, IFI35 and EIF2AK2, were identified as prognostic genes for BRCA related to SLE. IFN pathway played an important role in the etiology of SLE and the prognosis of BRCA.Copyright © 2023 Elsevier GmbH. All rights reserved.