Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Preventive Medicine, School of Public Health, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Immunobiology. 2023 Sep;228(5):152730. doi: 10.1016/j.imbio.2023.152730. Epub 2023 Aug 10.
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.
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 患乳腺癌（BRCA）的风险降低。因此，我们试图通过整合分析和机器学习来寻找与 SLE 相关的 BRCA 的预后基因。
首先，我们从基因表达综合数据库（GEO）下载了 2 个 SLE 数据集和从癌症基因组图谱（TCGA）下载了 BRCA 数据。随后，我们通过 Metascape 在 SLE 中进行差异表达基因（DEGs）和功能富集分析。在两个数据集都有差异表达的基因是验证的 DEGs。构建 PPI 网络后，与 BRCA 中的生存基因相交得到候选基因。然后，通过lasso 回归在训练集和验证集中验证候选基因，得到预后基因。之后，我们研究了预后基因对 SLE 的诊断潜力和对 BRCA 预后的预测疗效。此外，对 SLE 和 BRCA 进行了 GSEA 分析和免疫浸润分析。最后，构建了预后基因-miRNAs 网络，并对共享基因进行了功能富集。
SLE 的 DEGs 主要富集于中性粒细胞脱颗粒和 IFN 途径。建立 BRCA 的lasso 模型后，IRF7、IFI35 和 EIF2AK2 被鉴定为与 SLE 相关的 BRCA 预后基因，对 BRCA 的预后具有良好的预测能力。预后基因对 SLE 具有很好的诊断潜力，IFI35 和 EIF2AK2 与 SLE 活动呈正相关，IRF7 与 IFI35 呈正相关。GSEA 表明 SLE 和 BRCA 均与泛素化降解有关。免疫浸润表明 SLE 中浆细胞、树突状细胞（DC）、中性粒细胞和单核细胞升高。BRCA 低危组中 DC、NK 和 CD8 T 细胞升高。最后，验证了 5 个共享 miRNA，主要富集于 IFN 途径。
IRF7、IFI35 和 EIF2AK2 被鉴定为与 SLE 相关的 BRCA 预后基因。IFN 途径在 SLE 的发病机制和 BRCA 的预后中起着重要作用。
