Deng Sisi, Kim Wooyong, Cheng Kefan, Yang Qianlu, Singh Yogesh, Bae Gyuntae, Bézière Nicolas, Mager Lukas, Kommoss Stefan, Sprengel Jannik, Trautwein Christoph
Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, University Hospital Tübingen, Tübingen, Germany.
Cluster of Excellence iFIT (EXC 2180) "Image Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany.
Cancer Metab. 2025 May 13;13(1):21. doi: 10.1186/s40170-025-00391-5.
Malignant ascites is a common complication of advanced ovarian cancer (OC) and gastrointestinal cancer (GI), significantly impacting metastasis, quality of life, and survival. Increased intestinal permeability can lead to blood or lymphatic infiltration and microbial translocation from the gastrointestinal or uterine tract. This study aimed to identify microbiota-derived metabolites in ascites from OC (stages II-III and IV) and GI patients, assessing their roles in tumor progression.
Malignant ascites samples from 18 OC and GI patients were analyzed using a four-dimensional (4D) untargeted metabolomics approach combining reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) with trapped ion mobility spectrometry time-of-flight mass spectrometry (timsTOF-MS). Additonally, a targeted flow cytometry-based cytokine panel was used to screen for inflammatory markers. Non-endogenous, microbiota-derived metabolites were identified through the Human Microbial Metabolome Database (MiMeDB).
OC stage IV exhibited metabolic profiles similar to GI cancers, while OC stage II-III differed significantly. Stage IV OC patients exhibited higher levels of 11 typically microbiome-derived metabolites, including 1-methylhistidine, 3-hydroxyanthranilic acid, 4-pyridoxic acid, biliverdin, butyryl-L-carnitine, hydroxypropionic acid, indole, lysophosphatidylinositol 18:1 (LPI 18:1), mevalonic acid, N-acetyl-L-phenylalanine, and nudifloramide, and lower levels of 5 metabolites, including benzyl alcohol, naringenin, o-cresol, octadecanedioic acid, and phenol, compared to stage II-III. Correlation analysis revealed positive associations between IL-10 and metabolites such as glucosamine and LPCs, while MCP-1 positively correlated with benzyl alcohol and phenol.
4D metabolomics revealed distinct metabolic signatures in OC and GI ascites, highlighting microbiota-derived metabolites involved in lipid metabolism and inflammation. Metabolites like 3-hydroxyanthranilic acid, indole, and naringenin may serve as markers of disease progression and underscore the microbiota's role in shaping malignant ascites and tumor biology.
恶性腹水是晚期卵巢癌（OC）和胃肠道癌（GI）的常见并发症，对转移、生活质量和生存有显著影响。肠道通透性增加可导致血液或淋巴浸润以及微生物从胃肠道或子宫途径的易位。本研究旨在鉴定OC（II - III期和IV期）和GI患者腹水中微生物群衍生的代谢物，评估它们在肿瘤进展中的作用。
使用结合反相（RP）和亲水相互作用液相色谱（HILIC）与阱式离子淌度质谱飞行时间质谱（timsTOF-MS）的四维（4D）非靶向代谢组学方法分析18例OC和GI患者的恶性腹水样本。此外，使用基于靶向流式细胞术的细胞因子检测板筛选炎症标志物。通过人类微生物代谢组数据库（MiMeDB）鉴定非内源性、微生物群衍生的代谢物。
IV期OC表现出与GI癌相似的代谢谱，而II - III期OC有显著差异。与II - III期相比，IV期OC患者表现出11种典型微生物群衍生代谢物的水平较高，包括1 - 甲基组氨酸、3 - 羟基邻氨基苯甲酸、4 - 吡啶甲酸、胆绿素、丁酰 - L - 肉碱、羟基丙酸、吲哚、溶血磷脂酰肌醇18:1（LPI 18:1）、甲羟戊酸、N - 乙酰 - L - 苯丙氨酸和裸花紫珠酰胺，以及5种代谢物水平较低，包括苯甲醇、柚皮素、邻甲酚、十八烷二酸和苯酚。相关性分析显示IL - 10与氨基葡萄糖和LPCs等代谢物之间呈正相关，而MCP - 1与苯甲醇和苯酚呈正相关。
4D代谢组学揭示了OC和GI腹水中不同的代谢特征，突出了参与脂质代谢和炎症的微生物群衍生代谢物。3 - 羟基邻氨基苯甲酸、吲哚和柚皮素等代谢物可能作为疾病进展的标志物，并强调微生物群在塑造恶性腹水和肿瘤生物学中的作用。
