Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery/Sarcoma Center, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
Department of International Medical Services (IMS), Beijing Tiantan Hospital of Capital Medical University, Beijing, People's Republic of China.
Ann Med. 2023;55(2):2242247. doi: 10.1080/07853890.2023.2242247.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant solid tumours, and abnormal metabolic reprogramming in the tumour microenvironment is regarded as an important contributor to its pathogenesis.
As there is an urgency to identify new targets based on the metabolic features that are highly refractory to PDAC treatment, this study aimed to identify suitable therapeutic targets for PDAC.
In this study, gene set enrichment and Kyoto Encyclopedia of Genes and Genomes analyses were performed on 163 PDAC tissue samples and 165 normal pancreatic tissue samples from The Cancer Genome Atlas and Genotype-Tissue Expression databases to identify alterations in critical metabolites that may contribute to PDAC pathogenesis. Furthermore, ultra-performance liquid chromatography-tandem mass spectrometry was performed to identify significant metabolic pathways between 24 pairs of tumour and adjacent non-tumour tissues and between serum samples from PDAC patients and healthy donors.
Fifty-one tissue metabolites and 26 serum metabolites were altered in PDAC. Among them, those in the γ-glutamyl cycle were the most substantially changed, and 5-oxoproline was the biomarker of PDAC with the most significantly decreased levels.
The γ-glutamyl cycle and 5-oxoproline might be potential biomarkers and therapeutic targets to improve the diagnosis, therapy, and prognosis of PDAC.
胰腺导管腺癌（PDAC）是最致命的恶性实体瘤之一，肿瘤微环境中的异常代谢重编程被认为是其发病机制的重要因素。
由于迫切需要根据对 PDAC 治疗具有高度抗性的代谢特征来确定新的靶点，本研究旨在确定 PDAC 的合适治疗靶点。
本研究对来自癌症基因组图谱和基因型-组织表达数据库的 163 个 PDAC 组织样本和 165 个正常胰腺组织样本进行了基因集富集和京都基因与基因组百科全书分析，以确定可能导致 PDAC 发病机制的关键代谢物的改变。此外，还进行了超高效液相色谱-串联质谱分析，以鉴定 24 对肿瘤和相邻非肿瘤组织以及 PDAC 患者和健康供体的血清样本之间的显著代谢途径。
PDAC 中改变了 51 种组织代谢物和 26 种血清代谢物。其中，γ-谷氨酰循环中的代谢物变化最大，5-氧脯氨酸是 PDAC 标志物，其水平降低最为显著。
γ-谷氨酰循环和 5-氧脯氨酸可能是改善 PDAC 的诊断、治疗和预后的潜在生物标志物和治疗靶点。
