基于生物信息学探讨术中放疗对Luminal型乳腺癌微环境影响

Exploring the Impact of Intraoperative Radiotherapy on the Microenvironment of Luminal-Type Breast Cancer Based on Bioinformatics

摘要: 目的：运用生物信息学分析术中放疗(Intraoperative Radiotherapy, IROT)对Luminal型乳腺癌免疫微环境的影响，筛选关键基因并探讨其可能的作用机制。方法：从GEO数据库下载GSE253650数据集，包含IORT组与非IORT组Luminal型乳腺癌组织的基因表达谱。用GEO2R筛选差异表达基因(differentially expressed genes, DEGs)，对DEGs进行基因本体(Gene ontology, GO)及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)以及基因富集分析(Gene Set Enrichment Analysis, GSEA)。通过STRING构建蛋白互作网络，Cytoscape筛选核心基因(hub基因)。GEPIA2和UALCAN验证hub基因表达及预后，筛选出SELL并分析其在不同亚型中的表达差异。用cBioPortal分析SELL突变特征及对总生存期的影响。HPA数据库检测SELL在乳腺癌和正常组织中的表达。TIMER数据库分析SELL表达与免疫细胞浸润的相关性。DSigDB数据库对SELL做药物筛选。结果：共筛出729个差异表达基因，其中上调443个、下调286个，SELL (L-selectin)在IORT组上调。GO分析显示差异基因富集在免疫受体活性、细菌防御反应、质膜外侧面；KEGG富集在细胞因子–细胞因子受体相互作用、IL-17信号通路等。GSEA富集在MHC II类抗原呈递通路、细胞因子-JAK-STAT通路等。蛋白互作网络筛出10个hub基因，SELL在Luminal B型中是保护因素(P < 0.05)。SELL在Luminal型中表达高于正常组织和HER2阳性亚型，且与多种免疫细胞浸润呈正相关(P < 0.05)。并筛出萘丁美酮、美洛昔康等10种潜在靶向药物。结论：SELL可能是IORT调控Luminal型乳腺癌组织免疫微环境的关键分子，可能通过介导免疫细胞募集参与肿瘤免疫重塑。SELL在Luminal B型中高表达，且与预后良好相关，有望成为潜在分子标志物和治疗靶点。

Abstract: Objective: This paper aims to investigate the impact of intraoperative radiotherapy (IORT) on the immune microenvironment of luminal-type breast cancer using bioinformatics analysis, identify key genes, and explore their potential mechanisms. Methods: The GSE253650 dataset was downloaded from the GEO database, containing gene expression profiles of luminal-type breast cancer tissues from IORT and non-IORT groups. Differentially expressed genes (DEGs) were identified using GEO2R. GO, KEGG, and GSEA enrichment analyses were performed on the DEGs. A protein-protein interaction network was constructed using STRING, and hub genes were screened using Cytoscape. Hub gene expression and prognostic value were validated using GEPIA2 and UALCAN. SELL was selected for further analysis, and its expression differences across breast cancer subtypes were examined. Mutation characteristics and overall survival associated with SELL were analyzed using cBioPortal. SELL expression in breast cancer and normal tissues was validated using the HPA database. The correlation between SELL expression and immune cell infiltration was analyzed using TIMER. Potential drugs targeting SELL were predicted using the DSigDB database. Results: A total of 729 DEGs were identified, including 443 upregulated and 286 downregulated genes. SELL (L-selectin) was upregulated in the IORT group. GO analysis showed that DEGs were enriched in immune receptor activity, defense response to bacterium, and external side of plasma membrane. KEGG enrichment revealed cytokine-cytokine receptor interaction and the IL-17 signaling pathway. GSEA identified enrichment in MHC class II antigen presentation and cytokine-JAK-STAT pathways. Ten hub genes were identified from the PPI network. SELL was found to be a protective factor in luminal B subtype breast cancer (P < 0.05). SELL expression was higher in luminal-type breast cancer than in normal tissues and HER2-positive subtype, and was positively correlated with the infiltration of multiple immune cell types (P < 0.05). Ten potential targeted drugs, including nabumetone and meloxicam, were identified. Conclusion: SELL may serve as a key molecule through which IORT modulates the immune microenvironment of luminal-type breast cancer, potentially participating in tumor immune remodeling by mediating immune cell recruitment. SELL is highly expressed in luminal B subtype breast cancer and is associated with favorable prognosis, making it a promising molecular marker and therapeutic target.