Background

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.

Method

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.

Result

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.

Conclusion

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.

中文翻译：

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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

背景

系统性红斑狼疮（SLE）是一种多器官受累的自身免疫性疾病，一些研究发现SLE可降低患乳腺癌（BRCA）的风险。因此，我们试图通过综合分析和机器学习来寻找与SLE相关的BRCA预后基因。

方法

首先，我们从基因表达综合 (GEO) 下载了 2 个 SLE 数据集，从癌症基因组图谱 (TCGA) 下载了 BRCA 数据。随后，我们通过 Metascape 在 SLE 中进行了差异表达基因 (DEG) 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 DEG。构建PPI网络后，将节点>30的基因与BRCA中的存活基因相交以获得候选基因。然后，通过套索回归在训练集和验证集中验证候选基因，以获得预后基因。随后，我们研究了 SLE 预后基因的诊断潜力以及 BRCA 预后的预测功效。此外，还对 SLE 和 BRCA 进行了 GSEA 分析和免疫浸润。最后，我们构建了一个预后基因-miRNA 网络，并对共享基因进行了功能富集。

结果

SLE 的 DEG 主要富含中性粒细胞脱颗粒和 IFN 途径。BRCA套索模型建立后，IRF7、IFI35和EIF2AK2被确定为与SLE相关的BRCA预后基因，对BRCA预后具有良好的预测能力。预后基因对 SLE 具有极好的诊断潜力，其中 IFI35 和 EIF2AK2 与 SLE 活动呈正相关，IRF7 与 IFI35 呈正相关。GSEA 显示 SLE 和 BRCA 均与泛素化降解相关。免疫浸润表明浆细胞、树突状细胞 (DC)、中性粒细胞和单核细胞在 SLE 中升高。BRCA 低风险组的DC、NK 和 CD8 ⁺ T 细胞升高。最终确认了5个共享miRNA，主要富集于IFN通路。

结论

IRF7、IFI35 和 EIF2AK2 被确定为与 SLE 相关的 BRCA 的预后基因。IFN通路在SLE的病因学和BRCA的预后中发挥重要作用。