Chromatographic matching: The retention time of analyte peaks in biological samples was consistent with corresponding authentic reference standards under identical UPLC gradient separation conditions; peak symmetry, peak width and peak shape were highly matched between sample peaks and standard peaks.
Mass spectrometric MRM transition matching: Precursor ion mass, characteristic fragment ion mass, optimized declustering potential (DP) and collision energy (CE) of each analyte were consistent with the parameter library established by pure reference compounds.Metabolites that simultaneously satisfied the above chromatographic and MS/MS matching criteria were regarded as positively identified target metabolites. Compounds without matching standard references were not annotated in this quantitative detection batch.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - alternating - hilic"],"chromatography_protocol":["Metabolite separation was carried out on an ExionLC™ AD ultra-performance liquid chromatography (UPLC) platform (SCIEX, Shanghai, China) integrated with a built-in temperature-controlled autosampler. Analyte separation relied on an ACQUITY BEH Amide analytical column (1.7 µm particle size, 100 mm × 2.1 mm internal diameter). No guard column was equipped for this analytical run.Mobile phase A was ultrapure water containing 2 mM ammonium acetate and 0.04% formic acid; mobile phase B was acetonitrile supplemented with 2 mM ammonium acetate and 0.04% formic acid. The flow rate was fixed at 0.4 mL/min; column oven temperature was maintained constantly at 40 °C; the injection volume of each sample was 2 μL.
"],"publication":["Glutamine-restricted diets restore sensitivity to KRASG12D inhibitor through the reversal of ANXA1-mediated metabolic reprogramming."],"submitter_name":["Jiatong Li"],"submitter_affiliation":["Shanghai Cancer Institute"],"organism_part":["Subcutaneous of nude mice"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["Frozen PDX tumor tissue samples were weighed (20 ± 2 mg per sample) and transferred into pre-cooled 2 mL homogenization tubes containing stainless steel grinding beads. Pre-chilled mixed extraction solvent (acetonitrile: methanol: ultrapure water = 2:2:1, v/v/v) was added at a solid-liquid ratio of 1:10 (mg/μL). Tissue homogenization was performed using a high-throughput tissue grinder at 50 Hz for 4 min, followed by 30 min incubation on ice to fully extract intracellular metabolites.
"],"organism":["Mus musculus"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS14825"],"author":["Jiatong Li. Shanghai Cancer Institute. lijiatong@renji.com."],"data_transformation_protocol":["Quantitative peak integration and data calibration were performed using MultiQuant 3.0.3 software (Version 3.0.3, SCIEX). Retention time and peak shape profiles of authentic chemical reference standards were set as matching benchmarks to align, integrate and calibrate chromatographic peaks of target metabolites detected in all PDX tumor samples.
"],"study_factor":["Treatment"],"submitter_email":["lijiatong@renji.com"],"sample_collection_protocol":["Patient-derived xenograft (PDX) tumor tissues subcutaneously implanted on nude mice (Mus musculus) were collected as analytical samples. Mice were sacrificed via cervical dislocation under deep anesthesia, and subcutaneous tumor masses were completely dissected and separated from normal mouse adipose and skin tissues on ice. Residual blood on tissue surfaces was rapidly washed off with pre-cooled phosphate buffered saline (PBS). All isolated tumor tissues were cut into small fragments, immediately snap-frozen in liquid nitrogen, and transferred to a −80 °C ultra-low temperature refrigerator for long-term storage to block endogenous metabolic enzyme activity and prevent metabolite degradation.
"],"omics_type":["Metabolomics"],"study_design":["Metabolomics","AB SCIEX QTRAP 6500+","Mus musculus","LC-MS","SCIEX ExionLC AD","targeted analysis","malignant pancreatic neoplasm","untargeted analysis","Subcutaneous of nude mice","Mice","experimental blank"],"curator_keywords":["Metabolomics","LC-MS","AB SCIEX QTRAP 6500+","Mus musculus","SCIEX ExionLC AD","targeted analysis","malignant pancreatic neoplasm","untargeted analysis","Subcutaneous of nude mice","Mice","experimental blank"],"mass_spectrometry_protocol":["The UPLC separation system was coupled to a QTRAP® 6500+ triple quadrupole tandem mass spectrometer (SCIEX, Shanghai, China) with electrospray ionization (ESI) interface. The ion source heater temperature was set to 550 °C. Ion spray voltage was adjusted to 5500 V under positive ion mode and −4500 V under negative ion mode; curtain gas (CUR) pressure was set to 35 psi.Multiple reaction monitoring (MRM) acquisition mode was adopted for quantitative detection. Each characteristic precursor-product ion pair of target metabolites was scanned under compound-specific optimized declustering potential (DP) and collision energy (CE). Raw LC-MS/MS data were acquired and stored using Analyst 1.6.3 software. Since no full-scan m/z range data were provided in original materials, MRM scheduled ion monitoring without fixed full scan mass window was applied for all target compounds.
"],"metabolite_name":["L-Phenylalanine","Glycyl-L-Proline","3,7-Dimethyluric Acid","N-Isovaleroylglycine","kynurenine","Guanidinoethyl Sulfonate","Creatine","N6-Acetyl-L-Lysine","L-Ornithine","4-Acetamidobutyric Acid","L-Isoleucine","N'-Formylkynurenine","N¦Á-Acetyl-L-Arginine","L-Threonine","5-Aminovaleric Acid","Anserine","L-Alanine","S-Sulfo-L-Cysteine","D-Homocysteine","L-Histidine","L-Leucine","L-Pipecolic Acid","L-Citrulline","L-Cystine","5-Hydroxy-Tryptamine","Succinic Acid","N-Glycyl-L-Leucine","2-Aminoethanesulfonic Acid","(5-L-Glutamyl)-L-Alanine","L-Proline","N-Propionylglycine","L-Methionine","Urea","3-N-Methyl-L-Histidine","L-Cystathionine","Phosphorylethanolamine","1,3-Dimethyluric Acid","L-Lysine","P-Aminohippuric Acid","N¦Á-Acetyl-L-glutamine","3-Chloro-L-Tyrosine","6-Aminocaproic Acid","argininosuccinic acid","Homoserine","L-Arginine","¦Á-Aminoadipic acid","Kynurenic Acid","O-Phospho-L-Serine","Glutathione Oxidized","Trans-4-Hydroxy-L-Proline","1-Methylhistidine","(S)-¦Â-Aminoisobutyric Acid","Glycine","N8-Acetylspermidine","glycylphenylalanine","Creatine Phosphate","2-Aminobutyric acid","L-Tryptophyl-L-glutamic acid","¦Ã-Aminobutyric Acid","L-Cysteine","L-¦Á-Aspartyl-L-phenylalanine","L-Carnosine","Methionine Sulfoxide","Nicotinuric Acid","L-Tryptophan","3-Hydroxyhippuric Acid","N-Acetyl-L-Tyrosine","S-(5-Adenosyl)-L-Homocysteine","¦Ã-Glutamate-Cysteine","L-Glutamic acid","L-Theanine","3-Aminoisobutanoic Acid","Ethanolamine","L-Homocystine","N,N-Dimethylglycine","5-Hydroxy-tryptophan","5-Hydroxylysine","Trimethylamine N-Oxide","N-Acetylneuraminic Acid","1,3,7-Trimethyluric Acid","3-Iodo-L-Tyrosine","D-Alanyl-D-Alanine","L-Glutamine","L-Tyrosine","L-tyrosine methyl ester","L-Homocitrulline","Beta-Alanine","Sarcosine","L-Serine","Homo-L-arginine","L-Valine","L-Aspartate","N-Acetylaspartate","L-Asparagine Anhydrous"],"additional_accession":[]},"is_claimable":false,"name":"Glutamine-restricted diets restore sensitivity to KRASG12D inhibitor through the reversal of ANXA1-mediated metabolic reprogramming","description":"This study investigates the mechanisms underlying KRASG12D inhibitor resistance and evaluates strategies to enhance treatment sensitivity. Our findings indicate that a glutamine-restricted diet not only reverses KRASG12D inhibitor resistance in PDAC but also achieves durable remission with long-term survival. Mechanistically, KRASG12D inhibitor resistance markedly upregulates ANXA1 expression, which, in turn, promotes its binding to the glutamine-related enzyme GOT1 and stabilizes its expression. Additionally, we find that ANXA1 up-regulation facilitates mitochondrial localization of GLS1, thereby altering glutamine metabolism. These findings highlight ANXA1-mediated glutamine metabolism as a key driver of KRASG12D inhibitor resistance and support glutamine-restricted diets as a potential therapeutic strategy for KRASG12D-mutant pancreatic ductal adenocarcinoma.","dates":{"publication":"2026-06-27","submission":"2026-06-22"},"accession":"MTBLS14825","cross_references":{}}