系统性红斑狼疮（SLE）患者患乳腺癌（BRCA）的风险较一般人群较低。本研究探讨了两种疾病中失调的潜在分子机制。采用来自基因表达图组（GEO）网站的SLE和BRCA数据集执行了加权基因共表达网络分析（WGCNA），并确认了膜金属内切肽酶（MME）在两种疾病中的潜在作用。然后，对相关蛋白质和miRNA进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，以探究潜在的分子途径。 WGCNA揭示了MME与SLE呈正相关，与BRCA呈负相关。在BRCA中，MME在肿瘤组织中表达显著降低，尤其在腺激素受体阳性B型和浸润性导管癌亚型中。接受者操作特征曲线（ROC）分析将MME识别为BRCA的有价值诊断生物标志物，曲线下面积（AUC）值为0.984（95%置信区间=0.976-0.992）。KEGG富集分析提示MME相关蛋白质和miRNA可能通过PI3K/AKT/FOXO信号通路降低SLE患者患BRCA的发病率。低MME表达与有利的无复发生存（RFS）但没有其他临床结局相关，并可能导致BRCA对化疗的耐药性，AUC值等于0.527（P值<0.05）。 总之，MME在BRCA中表达显著降低，与SLE呈正相关，可能通过PI3K/AKT/FOXO信号通路降低SLE患者患BRCA的发病率。 版权所有：©2023 Ding等。本文是一篇在创作共享许可下发行的开放存取文章，许可协议允许用户自由使用、发布和复制，但必须注明原作者和来源。

Patients with systemic lupus erythematosus (SLE) have a lower risk of breast cancer (BRCA) than the general population. In this study, we explored the underlying molecular mechanism that is dysregulated in both diseases.Weighted gene coexpression network analysis (WGCNA) was executed with the SLE and BRCA datasets from the Gene Expression Omnibus (GEO) website and identified the potential role of membrane metalloendopeptidase (MME) in both diseases. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of related proteins and miRNAs were performed to investigate the potential molecular pathways.WGCNA revealed that MME was positively related to SLE but negatively related to BRCA. In BRCA, MME expression was significantly decreased in tumor tissues, especially in luminal B and infiltrating ductal carcinoma subtypes. Receiver operating characteristic (ROC) analysis identified MME as a valuable diagnostic biomarker of BRCA, with an area under the curve (AUC) value equal to 0.984 (95% confidence interval = 0.976-0.992). KEGG enrichment analysis suggested that MME-related proteins and targeted miRNAs may reduce the incidence of BRCA in SLE patients via the PI3K/AKT/FOXO signaling pathway. Low MME expression was associated with favorable relapse-free survival (RFS) but no other clinical outcomes and may contribute to resistance to chemotherapy in BRCA, with an AUC equal to 0.527 (P value < 0.05).In summary, MME expression was significantly decreased in BRCA but positively correlated with SLE, and it might reduce the incidence of BRCA in SLE patients via the PI3K/AKT/FOXO signaling pathway.Copyright: © 2023 Ding et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.