乳腺癌年全球新病例超过180万例，及时诊断和治疗对于预防死亡至关重要。坏死程序化细胞死亡（necroptosis）被认为是乳腺癌细胞凋亡的重要途径，但其与乳腺癌进展和分子机制的关系尚未得到充分探索。本研究旨在采用综合的生物信息学分析方法，结合药物敏感性评估，探讨乳腺癌中坏死程序化相关基因的分子特征和临床预后价值。将TCGA和GEO数据库中与乳腺癌相关的转录组、临床数据和肿瘤突变负荷（TMB）数据整合，从GSEA网站下载坏死程序化基因集进行分析。筛选条件设定为调整后P值<0.05 和 |log2FC(fold change)|>0.585，以筛选与乳腺癌坏死程序化相关的差异表达基因。对乳腺癌坏死程序化基因进行生存预后分析。此外，还对与预后相关的坏死程序化基因进行进一步分析，包括免疫浸润分析和GO/KEGG富集分析，以探索乳腺癌坏死程序化基因的潜在生物学功能和信号通路机制。对预后相关的坏死程序化基因进行药物敏感性筛选，以找出促进坏死程序化基因表达的潜在药物，最终对获得的核心靶基因进行单基因分析。 通过综合生物信息学分析，鉴定到与BRCA-Necroptosis相关的29个差异表达的mRNA，其中包括18个上调mRNA和11个下调mRNA。此外，差异基因的单因素分析显示，HSPA4、PLK1、TNFRSF1B、FLT3和LEF1的表达与BRCA的生存预后密切相关。基于这些基因的表达构建了乳腺癌预后模型，发现坏死程序化风险基因曲线的曲线下面积（AUC）最大，表明这些基因对BRCA的发生和预后具有一定的临床预测意义。此外，具有不同坏死程序化基因表达的BRCA患者的临床特征存在显著差异。进一步GSVA和免疫浸润分析显示，坏死程序化差异表达基因主要通过参与免疫功能（如APC共抑制、APC共刺激、CCR、检测点）以及浸润的免疫细胞（如B细胞幼稚型、浆细胞和T细胞CD8等）影响BRCA的发生和进展。此外，坏死程序化基因组列图显示了1年生存率为0.979，3年生存率为0.883，5年生存率为0.774。坏死程序化基因组和列图是评估BRCA预后的重要指标。最后，对BRCA-Necroptosis基因进行药物敏感性筛选，发现A-770041、AC220、AP-24534、Bexarotene和BMS-509744等化合物作为潜在靶向药物对治疗BRCA坏死程序化基因具有一定的影响。坏死程序化基因与乳腺癌的发病和进展密切相关，并被认为影响BRCA个体的预后和药物治疗反应。因此，了解这些基因在乳腺癌中的作用可能有助于确定更精确和有效的治疗靶点。 版权所有© Bentham Science Publishers; 有任何问题，请发送邮件至epub@benthamscience.net。

Breast cancer accounts for over 1.8 million new cases worldwide annually, and prompt diagnosis and treatment are imperative to prevent mortality. Necroptosis, a form of programmed cell death, is thought to be a critical pathway for cancer cell apoptosis, yet, its relationship with breast cancer progression and molecular mechanisms remains largely unexplored.Our study aims to investigate the molecular characteristics and clinical prognostic value of necroptosis-related genes in breast cancer using a comprehensive approach that involves integrated bioinformatics analysis along with drug sensitivity assessment.Transcriptional, clinical, and tumor mutation burden (TMB) data related to breast cancer from the TCGA and GEO databases were integrated, and the necroptosis gene set was downloaded from the GSEA website for analysis. The screening conditions were set as adjusted P<0.05 and |log2FC(fold change)|>0.585 to screen for differential expression genes related to breast cancer necroptosis. Survival prognosis analysis was conducted on breast cancer necroptosis genes. Further analysis was conducted on prognosis-related necroptosis genes, including immune infiltration analysis and GO/KEGG enrichment analysis, to explore the potential biological functions and signaling pathway mechanisms of breast cancer necroptosis genes. Drug sensitivity screening was conducted on the prognosis-related necroptosis to identify potential drugs that target the promotion of necroptosis gene expression, and ultimately, single-gene analysis was performed on the core target genes obtained.Through integrated bioinformatics analysis, 29 differentially expressed mRNAs related to BRCA-Necroptosis were identified, including 18 upregulated mRNAs and 11 downregulated mRNAs. In addition, single-factor analysis of differential genes showed that the expression of HSPA4, PLK1, TNFRSF1B, FLT3, and LEF1 was closely related to BRCA survival prognosis. Based on the expression of these genes, a breast cancer prognosis model was constructed, and it was found that the area under the curve (AUC) of the curve of the risk genes for necroptosis was the largest, indicating that these genes have a certain clinical predictive significance for the occurrence and prognosis of BRCA. Additionally, there were significant differences in clinical characteristics of BRCA patients with different necroptosis gene expressions. Furthermore, GSVA and immune infiltration analysis revealed that Necroptosis-DEGs mainly affect the occurrence and progression of BRCA by participating in immune functions such as APC co-inhibition, APC co-stimulation, CCR, checkpoint, as well as infiltrating immune cells such as B cells naive, plasma cells, and T cells CD8. Moreover, the necroptosis gene group column chart indicated a 1-year survival rate of 0.979, a 3-year survival rate of 0.883, and a 5-year survival rate of 0.774. The necroptosis gene group and column chart are important indicators for evaluating BRCA prognosis. Finally, drug sensitivity screening of BRCA-Necroptosis genes showed that compounds such as A-770041, AC220, AP-24534, Bexarotene, and BMS-509744 have certain effects as potential targeted drugs for the treatment of BRCA necroptosis genes.Necroptosis genes are implicated in the pathogenesis and progression of breast cancer and are thought to impact the prognosis and response to drug treatments in individuals with BRCA. Consequently, understanding the role of these genes in breast cancer may aid in identifying more precise and efficacious therapeutic targets.Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.