Metabolite identification was based on MRM transitions, retention time matching, and authentic standards. Target metabolites were confirmed by comparing retention times and ion pair ratios with reference standards analyzed under identical LC-MS conditions. The standard mixture in the sample queue was used for retention time correction. For compounds without standards, identification relied on accurate MRM transitions and database matching. Confirmed metabolites were reported with transition ions, retention times, and quantification results.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - alternating - reverse-phase"],"chromatography_protocol":["Samples were separated using an Agilent 1290 Infinity LC ultra-high-performance liquid chromatography system. The samples were placed in an autosampler at 4 °C, and the column temperature was maintained at 35 °C. Mobile phase A consisted of 50 mM ammonium acetate aqueous solution with 1.2% ammonium hydroxide, while mobile phase B consisted of 1% acetylacetone in acetonitrile. The flow rate was 300 μL/min, and the injection volume was 2 μL. The relevant liquid chromatography gradient was as follows: 0-1 min, 70% B; 1-10 min, B linearly changed from 70% to 60%; 10-12 min, B linearly changed from 60% to 30%; 12.1-15 min, B was maintained at 30%; 15-15.5 min, B linearly changed from 30% to 70%; 15.1-22 min, B was maintained at 70%. In the sample queue, a QC sample was set at regular intervals among the experimental samples to monitor and evaluate the stability and reproducibility of the system. A standard mixture of the target substances was also included in the sample queue for correction of chromatographic retention times.
"],"publication":["GDF15 hijacks B cells to fuel the lifeblood of tumor salvage pyrimidine synthesis."],"submitter_name":["junhu yuan"],"submitter_affiliation":["National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College"],"organism_part":["liver","supernatant"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Samples were retrieved from -80 °C, and 15 mg of each sample was weighed. Then, 200 μL of water and MP were added, followed by vortexing for 60 s. Next, 800 μL of methanol-acetonitrile solution (1:1, v/v) was added, followed by 10 μL of SUCCINIC ACID-D6 internal standard, and the mixture was vortexed for 60 s. The samples were subjected to low-temperature ultrasonication for 30 min, and this step was repeated twice. Afterwards, the samples were placed at -20 °C for 1 h to precipitate proteins, followed by centrifugation at 14,000 rcf for 20 min at 4 °C. The supernatant was collected and freeze-dried, and the samples were stored at -80 °C.
"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS15820"],"author":["junhu yuan. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. jhyuan1998@163.com."],"data_transformation_protocol":["Raw data acquired from the 5500 QTRAP ESI source in MRM mode were processed using Analyst and MultiQuant software. Peak integration was performed with a consistent retention time window across all samples. QC samples were used to monitor system stability and reproducibility. Metabolite concentrations were calculated from calibration curves and normalized to internal standards and sample weight. Data were filtered to remove peaks with poor reproducibility or signal-to-noise ratio below the threshold before statistical analysis.
"],"study_factor":["Treatment"],"submitter_email":["jhyuan1998@163.com"],"sample_collection_protocol":["Equal weights of mouse liver tumor tissues were rinsed with PBS and immediately placed into liquid nitrogen.
"],"omics_type":["Metabolomics"],"study_design":["Pyrimidine metabolism","Metabolomics","Mus musculus","targeted analysis","liver","GDF15","AB SCIEX QTRAP 5500","B cells","Agilent 1290 Infinity HPLC","supernatant","DHODH"],"curator_keywords":["Pyrimidine metabolism","Metabolomics","Mus musculus","targeted analysis","liver","GDF15","AB SCIEX QTRAP 5500","B cells","Agilent 1290 Infinity HPLC","supernatant","DHODH"],"mass_spectrometry_protocol":["Mass spectrometry analysis was performed using a 5500 QTRAP mass spectrometer (SCIEX) in negative ion mode. The 5500 QTRAP ESI source conditions were as follows: source temperature 450 °C, Ion Source Gas1 (Gas1): 45, Ion Source Gas2 (Gas2): 45, Curtain gas (CUR): 30, ionSapary Voltage Floating (ISVF) -4500 V. MRM mode was used to detect the target ion pairs.
"],"metabolite_name":["3-Phosphoglycerate","D-Ribulose 5-phosphate","alpha-Ketoglutarate","Dihydroxyacetone phosphate","Oxaloacetate","Thiamine pyrophosphate (TPP)","Thymideine-monophosphate (dTMP)","Fructose 1,6-bisphosphate","Histidine","Uridine diphosphate glucose","Threonine","Succinate","Methionine","2-Ketobutyric acid","Citrulline","Nicotinamide riboside","UDP-Glucuronate","Lysine","Nicotinamide","Adenosine-5'-diphosphate (ADP)","Glucosamine","Flavin mononucleotide (FMN)","N-Acetylglucosamine 6-phosphate","beta-Nicotinamide adenine dinucleotide (NAD)","Glycine","Guanine","Arginine","Succinic acid semialdehyde","Guanosine 5'-triphosphate (GTP)","Glycolic acid","Pyroglutamic acid","Glucosamine 6-phosphate","Creatinine","Alanine","Phenylalanine","Tryptophan","Aspartate","Uridine 5'-monophosphate","S-Adenosylmethionine","2-Hydroxybutanoic acid","Fructose 6-phosphate","ADP-ribose","D-Sedoheptulose 7-phosphate","Fumarate","Valine","Choline","Asparagine","Gamma-Aminobutyric acid","Uracil","N-Acetylneuraminic acid","Adenosine-5'-triphosphate (ATP)","Glycerol 3-phosphate","Lactate","Guanosine","Citrate","Creatine","Nicotinamide ribotide","Itaconic acid","Methylmalonic acid","Glucose 6-phosphate","Betaine","Adenosine monophosphate (AMP)","Maleic acid","Flavin adenine dinucleotide (FAD)","Glyceric acid","Gluconic acid","Tyrosine","Cis-Aconitate","Glutamate","S-Adenosylhomocysteine","Oxidized glutathione","Malate","Oxalic acid","Isocitrate","Uridine","Hydroxypropionic acid","Hypoxanthine","Ornithine","Adenosine-3',5'-cyclic monophosphate (cAMP)","D-Glucose","Guanosine diphosphate (GDP)","6-Phosphogluconate","Serine","2-Hydroxyglutarate","1,4-Dihydronicotinamide adenine dinucleotide (NADH)","Proline","Leucine","Glyoxylic acid","Uridine 5'-diphosphate","Ribose","UDP-N-acetylglucosamine","Isoleucine","Glucuronic acid","Adenosine","Adenine","Pyruvate","Guanosine monophosphate (GMP)","Fructose","N-Acetylglucosamine 1-phosphate","beta-Nicotinamide adenine dinucleotide phosphate (NADP)","Citraconic acid","D-Erythrose 4-phosphate","Inosine","3-Hydroxybutyric acid","Dimethylglycine","Glutamine"],"additional_accession":[]},"is_claimable":false,"name":"GDF15 hijacks B cells to fuel the lifeblood of tumor salvage pyrimidine synthesis","description":"B cell-tumor crosstalk has emerged as a critical determinant of tumor progression; however, its role in metabolic reprogramming and therapeutic resistance remains poorly understood. Here, we uncover a metabolic feedback loop that drives resistance to dihydroorotate dehydrogenase (DHODH) inhibitors. Mechanistically, DHODH inhibition induces lactylation of TERF2IP at lysine 208 (K208) in tumor cells, enabling TERF2IP to scaffold IKK and p65, thereby promoting p65 phosphorylation and subsequent GDF15 expression. Secreted GDF15 recruits B cells into the tumor microenvironment, where they activate JAK1-STAT3-IL-1beta signaling, which in turn enhances ERK-cMYC-UCK2-driven salvage pyrimidine synthesis and confers resistance to DHODH inhibition. Through high-throughput screening, we identify melitracen as a synergistic agent that reverses this B cell-dependent resistance. Collectively, our findings delineate a B cell-orchestrated regulatory axis governing tumor pyrimidine metabolism that underlies DHODH inhibitor resistance, and propose a clinically translatable combinatorial therapeutic strategy for cancer treatment.","dates":{"publication":"2026-09-27","submission":"2026-09-27"},"accession":"MTBLS15820","cross_references":{"HMDB":["HMDB0000223","HMDB0000243","HMDB0001406","HMDB0000134","HMDB0000300","HMDB0000157","HMDB0000050","HMDB0000296","HMDB0000064","HMDB0000562","HMDB0341410","HMDB0000195","HMDB0000283","HMDB0000159","HMDB0000929","HMDB0000190","HMDB0000011","HMDB0000133","HMDB0000176","HMDB0000696","HMDB0000043","HMDB0000058","HMDB0000115","HMDB0000700","HMDB0000122","HMDB0000660","HMDB0000097","HMDB0000883","HMDB0000158","HMDB0000092","HMDB0000267","HMDB0000162","HMDB0000139","HMDB0000161","HMDB0000167","HMDB0000123","HMDB0000641","HMDB0000177","HMDB0000208","HMDB0000112","HMDB0000187","HMDB0000168","HMDB0000230","HMDB0000939","HMDB0002092","HMDB0000904","HMDB0000625","HMDB0000254","HMDB0059655","HMDB0000148","HMDB0001248","HMDB0000156","HMDB0000191","HMDB0001520","HMDB0002329","HMDB0001227","HMDB0001185","HMDB0001178","HMDB0001473","HMDB0000045","HMDB0000126","HMDB0000902","HMDB0000290","HMDB0000072","HMDB0000288","HMDB0001341","HMDB0000286","HMDB0000229","HMDB0000124","HMDB0000094","HMDB0000807","HMDB0001397","HMDB0001254","HMDB0000295","HMDB0000538","HMDB0001401","HMDB0000214","HMDB0000517","HMDB0001201","HMDB0000935","HMDB0001372","HMDB0001068","HMDB0000217","HMDB0001316","HMDB0000182","HMDB0001058","HMDB0003337","HMDB0000202","HMDB0000634","HMDB0001321","HMDB0001367","HMDB0000855","HMDB0000127","HMDB0000618","HMDB0000119","HMDB0001259","HMDB0000005","HMDB0002817","HMDB0000132","HMDB0001514","HMDB0001273","HMDB0000687","HMDB0000172","HMDB0000034","HMDB0001487","HMDB0000193"]}}