在这项研究中，我们研究了与卵巢癌患者化疗临床反应相关的代谢变化。对来自对 NACT 反应较差 (PR) 或良好反应 (ER) 的高级别浆液性卵巢癌 (HGSC) 患者的新辅助化疗 (NACT) 前和后组织进行了检查。对根据严格的腹腔镜分类算法收集的 HGSC 组织切片进行解吸电喷雾电离质谱 (DESI-MS)。对 NACT 前样品的一个亚组进行了基于 MS 的定量蛋白质组学和磷酸化蛋白质组学。 NACT前PR肿瘤中高度丰富的代谢物与上皮区域的嘧啶代谢和基质区域缺氧诱导因子α的氧依赖性脯氨酸羟基化有关。 NACT后PR肿瘤上皮区更丰富的代谢物参与核苷酸代谢，NACT后PR肿瘤间质区更丰富的代谢物与天冬氨酸和天冬酰胺代谢、苯丙氨酸和酪氨酸代谢、核苷酸生物合成有关和尿素循环。基于不同丰度离子构建的预测模型可以将患者的肿瘤反应分类为 ER 或 PR，准确度为 75%（10 倍交叉验证岭回归模型）。这些发现提供了与化疗差异反应相关的新见解，并可能导致新的可操作目标。© 2023。作者。

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline hydroxylation of hypoxia-inducible factor alpha in the stromal regions. Metabolites more abundant in the epithelial regions of post-NACT PR tumors were involved in the metabolism of nucleotides, and metabolites more abundant in the stromal regions of post-NACT PR tumors were related to aspartate and asparagine metabolism, phenylalanine and tyrosine metabolism, nucleotide biosynthesis, and the urea cycle. A predictive model built on ions with differential abundances allowed the classification of patients' tumor responses as ER or PR with 75% accuracy (10-fold cross-validation ridge regression model). These findings offer new insights related to differential responses to chemotherapy and could lead to novel actionable targets.© 2023. The Author(s).