本研究的目的是通过生物信息学和孟德尔随机化 (MR) 分析来探讨丙酮酸代谢与乳腺癌 (BC) 之间的因果关系，以及关键代谢基因的分子作用。我们检索并检查了来自 GEO 的不同数据集数据库通过差异表达分析确定 BC 中的差异作用基因 (DAG)。随后，我们进行了功能和通路富集分析，以确定 BC 中值得注意的分子功能和代谢通路。通过 MR 分析，我们建立了丙酮酸代谢与 BC 易感性之间的因果关系。此外，利用 DGIdb 数据库，我们确定了作用于丙酮酸代谢途径相关基因的潜在靶向药物，并在 BC 制定了竞争性内源 RNA (ceRNA) 调控网络。我们收集了数据集 GSE54002、GSE70947 和 GSE22820，并确定了BC组和NC组之间总共有1127个DEG。 GO和KEGG富集分析显示，这些DEG的分子功能主要包括有丝分裂核分裂、细胞外基质、信号受体激活剂活性等。代谢途径主要集中在PI3K-Akt信号通路、细胞因子-细胞因子受体结合以及丙酮酸、酪氨酸等。此外，MR分析证明丙酮酸代谢与BC风险之间存在因果关系。最后，我们构建了通路基因（ADH1B、ACSS2、ACACB、ADH1A、ALDH2和ADH1C）与靶向药物之间的调控网络，以及BC的ceRNA（lncRNA-miRNA-mRNA）调控网络，进一步揭示了它们的相互作用。我们的研究揭示了丙酮酸代谢与 BC 风险之间的因果关系，发现 ADH1B、ACSS2、ACACB、ADH1A、ALDH2 和 ADH1C 在与丙酮酸代谢相关的分子机制中在 BC 的发展中发挥着重要作用，并确定了一些潜在的靶向小分子药物。© 2024。作者。

The study purpose was to explore the causal association between pyruvate metabolism and breast cancer (BC), as well as the molecular role of key metabolic genes, by using bioinformatics and Mendelian randomization (MR) analysis.We retrieved and examined diverse datasets from the GEO database to ascertain differentially acting genes (DAGs) in BC via differential expression analysis. Following this, we performed functional and pathway enrichment analyses to ascertain noteworthy molecular functions and metabolic pathways in BC. Employing MR analysis, we established a causal association between pyruvate metabolism and the susceptibility to BC. Additionally, utilizing the DGIdb database, we identified potential targeted medications that act on genes implicated in the pyruvate metabolic pathway and formulated a competing endogenous RNA (ceRNA) regulatory network in BC.We collected the datasets GSE54002, GSE70947, and GSE22820, and identified a total of 1127 DEGs between the BC and NC groups. GO and KEGG enrichment analysis showed that the molecular functions of these DEGs mainly included mitotic nuclear division, extracellular matrix, signaling receptor activator activity, etc. Metabolic pathways were mainly concentrated in PI3K-Akt signaling pathway, Cytokine-cytokine receptor binding and Pyruvate, Tyrosine, Propanoate and Phenylalanine metabolism, etc. In addition, MR analysis demonstrated a causal relationship between pyruvate metabolism and BC risk. Finally, we constructed a regulatory network between pathway genes (ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C) and targeted drugs, as well as a ceRNA (lncRNA-miRNA-mRNA) regulatory network for BC, further revealing their interactions.Our research revealed a causal association between pyruvate metabolism and BC risk, found that ADH1B, ACSS2, ACACB, ADH1A, ALDH2, and ADH1C takes place an important part in the development of BC in the molecular mechanisms related to pyruvate metabolism, and identified some potential targeted small molecule drugs.© 2024. The Author(s).