Cancer metabolomics has become a powerful way of understanding tumor biology, identifying biomarkers and metabolites, and helping precision oncology. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), among many other analytical platforms, has gained popularity over the past two and a half decades due to its unique ability of directly analyzing metabolites in tissue with spatial resolution. This review will study 2000–2025 MALDI-based strategies for cancer metabolite detection, spanning from early proof-of-concept protein profiling to the development of high-resolution MALDI-MS imaging (MALDI-MSI), which is capable of mapping thousands of metabolites at near single-cell resolution. Its applications include the differentiation of tumor versus normal tissue, discovery of stage and subtype specific biomarkers, mapping of metabolic heterogeneity, and the visualization of drug metabolism in situ. Breakthrough technological milestones, such as the advanced matrices, on-tissue derivatization, MALDI-2 post-ionization, and the integration with Orbitrap or Fourier-transform ion cyclotron resonance (FT-ICR) platforms, have significantly improved the overall sensitivity, metabolite coverage, and spatial fidelity. Clinically, MALDI-MS has shown its purpose in breast, prostate, colorectal, lung, and liver cancers by providing metabolic fingerprints that are linked to tumor microenvironments, hypoxia, and therapeutic response. However, challenges such as the inclusion of matrix interface with low-mass metabolites, limited quantitation, ion suppression, and the lack of standardized procedures do not yet allow for the transition from translation to routine diagnostics. Even with these hurdles, the future of MALDI-MS in oncology remains in a good position with major advancements in multimodal imaging, machine learning-based data integration, portable sampling devices, and clinical validation studies that are pushing the field towards precision treatment.
癌症代谢组学已成为理解肿瘤生物学、识别生物标志物和代谢物，并助力精准肿瘤学的重要方法。在众多分析平台中，基质辅助激光解吸/电离质谱（MALDI-MS）凭借其直接分析组织中代谢物并具备空间分辨率的独特优势，在过去二十五年间日益受到青睐。本综述将梳理2000年至2025年间基于MALDI的癌症代谢物检测策略，涵盖从早期概念验证性蛋白质谱分析，到能够以近单细胞分辨率绘制数千种代谢物分布的高分辨率MALDI质谱成像（MALDI-MSI）技术的发展历程。其应用包括区分肿瘤与正常组织、发现分期及亚型特异性生物标志物、绘制代谢异质性图谱以及原位可视化药物代谢过程。先进基质、组织上衍生化、MALDI-2后电离技术，以及与Orbitrap或傅里叶变换离子回旋共振（FT-ICR）平台的整合等突破性技术里程碑，显著提升了整体检测灵敏度、代谢物覆盖范围和空间保真度。在临床层面，MALDI-MS通过提供与肿瘤微环境、缺氧状态及治疗反应相关的代谢指纹图谱，已在乳腺癌、前列腺癌、结直肠癌、肺癌和肝癌中展现出应用价值。然而，基质与低质量代谢物信号干扰、定量能力有限、离子抑制效应以及标准化流程缺失等挑战，仍阻碍着该技术从转化研究向常规诊断的过渡。尽管存在这些障碍，随着多模态成像、基于机器学习的数据整合、便携式采样设备及临床验证研究等领域的重大进展推动该领域向精准治疗迈进，MALDI-MS在肿瘤学中的应用前景依然广阔。
Detection of Protein and Metabolites in Cancer Analyses by MALDI 2000–2025
肿瘤(癌症)患者之家