与 2D 单层模型相比，3D 多细胞肿瘤球体 (MTS) 模型在复制肿瘤微环境方面表现出增强的保真度，并且对临床药物具有出色的耐受性。在本研究中，我们使用多组学（转录组、蛋白质组和代谢组）工具来探索两种培养模型的分子机制和代谢差异。基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集途径分析表明，两种培养模型之间差异表达的基因主要富集于与细胞外基质、细胞外结构组织和线粒体相关的细胞成分和生物过程。功能。对三个组学数据的综合分析揭示了 11 个可能的耐药靶点。在这些靶标中，AKR1B1、ALDOC、GFPT2、GYS1、LAMB2、PFKFB4 和 SLC2A1 七个基因表现出显着的上调。相反，COA7、DLD、IFNGR1 和 QRSL1 四个基因显着下调。使用TCGA生存数据库进行的临床预后分析表明，SLC2A1、ALDOC和PFKFB4的高表达组与患者生存呈显着负相关。我们进一步验证了它们与化疗耐药性的关系，表明它们在改善预后和化疗结果方面的潜在意义。这些结果为潜在治疗靶点提供了宝贵的见解，有可能提高治疗效果和患者结果。© 2024 Wiley‐VCH GmbH。

The 3D multicellular tumor spheroid (MTS) model exhibits enhanced fidelity in replicating the tumor microenvironment and demonstrates exceptional resistance to clinical drugs compared to the 2D monolayer model. In this study, we used multiomics (transcriptome, proteomics, and metabolomics) tools to explore the molecular mechanisms and metabolic differences of the two culture models. Analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways revealed that the differentially expressed genes between the two culture models were mainly enriched in cellular components and biological processes associated with extracellular matrix, extracellular structural organization, and mitochondrial function. An integrated analysis of three omics data revealed 11 possible drug resistance targets. Among these targets, seven genes, AKR1B1, ALDOC, GFPT2, GYS1, LAMB2, PFKFB4, and SLC2A1, exhibited significant upregulation. Conversely, four genes, COA7, DLD, IFNGR1, and QRSL1, were significantly downregulated. Clinical prognostic analysis using the TCGA survival database indicated that high-expression groups of SLC2A1, ALDOC, and PFKFB4 exhibited a significant negative correlation with patient survival. We further validated their involvement in chemotherapy drug resistance, indicating their potential significance in improving prognosis and chemotherapy outcomes. These results provide valuable insights into potential therapeutic targets that can potentially enhance treatment efficacy and patient outcomes.© 2024 Wiley‐VCH GmbH.