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综合代谢组学和转录组学分析揭示了三阴性乳腺癌失调的网络和潜在生物标志物。

Comprehensive analysis of the metabolomics and transcriptomics uncovers the dysregulated network and potential biomarkers of Triple Negative Breast Cancer.

机构信息

The Clinical Laboratory Center, the Second Affiliated Hospital of Fujian Medical University, Quanzhou, P.R. China.

College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, P.R. China.

出版信息

J Transl Med. 2024 Nov 11;22(1):1016. doi: 10.1186/s12967-024-05843-y.

DOI:10.1186/s12967-024-05843-y
PMID:39529035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11552364/
Abstract

Triple-negative breast cancer (TNBC) is known for its aggressive nature, lack of effective diagnostic tools and treatments, and generally poor prognosis. The objective of this study was to investigate metabolic changes in TNBC using metabolomics approaches and explore the underlying mechanisms through integrated analysis with transcriptomics. In this study, serum untargeted metabolic profiles were first examined between 18 TNBC patients and 21 healthy control (HC) subjects using liquid chromatography-mass spectrometry (LC-MS), identifying a total of 22 significantly differential metabolites (DMs). Subsequently, receiver operating characteristic analysis revealed that 7-methylguanine could serve as a potential biomarker for TNBC in both the discovery and validation sets. Additionally, transcriptomic datasets were retrieved from the GEO database to identify differentially expressed genes (DEGs) between TNBC and normal tissues. An integrative analysis of the DMs and DEGs was conducted, uncovering potential molecular mechanisms underlying TNBC. Notably, three pathways-tyrosine metabolism, phenylalanine metabolism, and glycolysis/gluconeogenesis-were enriched, providing insight into the energy metabolism disorders in TNBC. Within these pathways, two DMs (4-hydroxyphenylacetaldehyde and oxaloacetic acid) and six DEGs (MAOA, ADH1B, ADH1C, AOC3, TAT, and PCK1) were identified as key components. In summary, this study highlights metabolic biomarkers that could potentially be used for the diagnosis and screening of TNBC. The comprehensive analysis of metabolomics and transcriptomics data offers a validated and in-depth understanding of TNBC metabolism.

摘要

三阴性乳腺癌(TNBC)以其侵袭性、缺乏有效的诊断工具和治疗方法以及普遍较差的预后而闻名。本研究的目的是使用代谢组学方法研究 TNBC 的代谢变化,并通过与转录组学的综合分析探索潜在的机制。在这项研究中,首先使用液相色谱-质谱联用(LC-MS)技术在 18 名 TNBC 患者和 21 名健康对照(HC)受试者之间检测血清非靶向代谢谱,共鉴定出 22 种显著差异代谢物(DMs)。随后,接受者操作特征分析显示,7-甲基鸟嘌呤可作为发现和验证集 TNBC 的潜在生物标志物。此外,还从 GEO 数据库中检索转录组数据集,以鉴定 TNBC 与正常组织之间的差异表达基因(DEGs)。对 DMs 和 DEGs 进行综合分析,揭示了 TNBC 潜在的分子机制。值得注意的是,三个途径——酪氨酸代谢、苯丙氨酸代谢和糖酵解/糖异生——被富集,为 TNBC 的能量代谢障碍提供了深入的了解。在这些途径中,两种 DMs(4-羟基苯乙醛和草酰乙酸)和六种 DEGs(MAOA、ADH1B、ADH1C、AOC3、TAT 和 PCK1)被确定为关键成分。总之,本研究强调了代谢标志物,它们可能被用于 TNBC 的诊断和筛查。代谢组学和转录组学数据的综合分析提供了对 TNBC 代谢的验证和深入理解。

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