胃癌（GC）是一种侵袭性疾病，由于缺乏易于诊断的工具、免疫疗法的抗性（由于PD-L1表达较低）或化疗（由于p53突变）以及併发症因素，特别是肌肉萎缩，导致晚期诊断。为了提高对这种复杂病理学的理解，我们建立了患者衍生的异种移植模型（PDX）并采用形态功能学方法（结合高分辨率成像和分子分析）对肿瘤生态系统进行表征，包括相关治疗生物标志物的表达和肌肉萎缩的存在。GC组织样本被植入裸鼠体内。建立的PDX接受了顺铂治疗或未接受治疗，并通过磁共振成像（MRI）进行成像，并通过转录组学分析进行相关生物标志物（p53、PD-L1、PD-1、HER-2、CDX2、CAIX、CD31、a-SAM）的表达分析。建立了三个良性、一个中等和一个恶性腺癌。所有模型都保留了它们原发性肿瘤的结构和组织学特征。MRI允许实时评估PDX之间的差异，包括亚结构、治疗后的变化和肌肉萎缩。免疫组化显示了模型和顺铂治疗之间p53、HER-2、CDX2、a-SAM、PD-L1、PD-1、CAIX和CD31的差异表达。转录组学揭示了治疗引起的低氧和代谢重编程环境。我们的PDX模型代表了人类肿瘤的多样性和复杂性，结构、组织学、肌肉萎缩和不同的生物标志物之间存在差异，这使得它们对铂类药物或新疗法对肿瘤及其微环境的影响分析具有价值。 © 2022年作者（S）。

Gastric cancer (GC) is an aggressive disease due to late diagnosis resulting from the lack of easy diagnostic tools, resistances toward immunotherapy (due to low PD-L1 expression), or chemotherapies (due to p53 mutations), and comorbidity factors, notably muscle atrophy. To improve our understanding of this complex pathology, we established patient-derived xenograft (PDX) models and characterized the tumor ecosystem using a morpho-functional approach combining high-resolution imaging with molecular analyses, regarding the expression of relevant therapeutic biomarkers and the presence of muscle atrophy.GC tissues samples were implanted in nude mice. Established PDX, treated with cisplatin or not, were imaged by magnetic resonance imaging (MRI) and analyzed for the expression of relevant biomarkers (p53, PD-L1, PD-1, HER-2, CDX2, CAIX, CD31, a-SAM) and by transcriptomics.Three well-differentiated, one moderately and one poorly differentiated adenocarcinomas were established. All retained the architectural and histological features of their primary tumors. MRI allowed in-real-time evaluation of differences between PDX, in terms of substructure, post-therapeutic changes, and muscle atrophy. Immunohistochemistry showed differential expression of p53, HER-2, CDX2, a-SAM, PD-L1, PD-1, CAIX, and CD31 between models and upon cisplatin treatment. Transcriptomics revealed treatment-induced hypoxia and metabolic reprograming in the tumor microenvironment.Our PDX models are representative for the heterogeneity and complexity of human tumors, with differences in structure, histology, muscle atrophy, and the different biomarkers making them valuable for the analyses of the impact of platinum drugs or new therapies on the tumor and its microenvironment.© 2022. The Author(s).